Embryology - User contributions [en-gb]

User:Z3330313

2011-10-28T07:09:03Z

Z3330313:

== Lab sign in ==

--[[User:Z3330313|z3330313]] 11:14, 2 August 2011 (EST)

--[[User:Z3330313|z3330313]] 12:52, 4 August 2011 (EST)

--[[User:Z3330313|z3330313]] 11:39, 11 August 2011 (EST)

--[[User:Z3330313|z3330313]] 12:45, 18 August 2011 (EST)

--[[User:Z3330313|z3330313]] 11:35, 1 September 2011 (EST)

--[[User:Z3330313|z3330313]] 11:42, 15 September 2011 (EST)

--[[User:Z3330313|z3330313]] 12:59, 22 September 2011 (EST)

--[[User:Z3330313|z3330313]] 12:33, 29 September 2011 (EST)

--[[User:Z3330313|z3330313]] 12:56, 6 October 2011 (EST)

--[[User:Z3330313|z3330313]]

--[[User:Z3330313|Joanna Pak]]

== [[LAB1]] ==

'''1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique.''''''

In Vitro Fertilisation is an ART (Assisted Reproduction technology) technique, used by infertile people. It is a
process whereby the egg is fertilised by the sperm outside the body. The first successful IVF baby named Louise
Brown was born in1978, the procedure was carried out by Patrick Steptoe and Robert Edwards. And in 2010 the Nobel
Prize was awarded to Robert Edwards for the development of in vitro fertilisation.
'''

'''2. Identify a recent paper on fertilisation and describe its key findings.''''''

"Not all sperm are equal: functional mitochondria characterize a subpopulation of human sperm with better fertilization potential."
<http://www.ncbi.nlm.nih.gov/pubmed/21448461>

This paper proves that not all sperm carry the potential to fertilise an egg. It found that mitochondrial activity plays a major role in the functionality of the sperm. They found that the level of mitochondrial function mirrored sperm quality. In conclusion, whatever the true biological role of sperm mitochondria in fertilization, mitochondrial activity is a clear hallmark of human sperm functionality.

'''3. Identify 2 congenital anomalies.'''

-Down syndrome
-Cystic fibrosis

--[--[[User:Z3330313|z3330313]] 17:31, 8 August 2011 (EST)] 17:30, 8 August 2011 (EST)] 12:52, 4 August 2011 (EST)

== [[LAB2]] ==

'''Identify the ZP protein that spermatozoa binds and how is this changed (altered) after fertilization.'''

The oocyte is surrounded by a glycoprotein membrane called the zone pellucida. It is the barrier that the spermatozoa has to push through to reach the oocyte for fertilisation. The zone pellucida protein 3 is the sperm receptor that the spermatozoa binds to as an pathway to enter the cell.
After fertilisation, a cortical reaction occurs where it modifies the ZP3 protein to an inactive form. Thus preventing more than one sperm from fertilising the egg.

--[[User:Z3330313|z3330313]] 15:57, 10 August 2011 (EST)

--[[User:Z3330313|z3330313]] 11:39, 11 August 2011 (EST)

===Lab3 Picture===

[[File:Differentially expressed RefSeq genes in human trisomy 21.jpg|thumb|Differentially expressed RefSeq genes in human trisomy 21]]

[[File:Differentially expressed RefSeq genes in human trisomy 21.jpg|350px]]

== [[Lab 3 Online Assessment]] ==

1. What is the maternal dietary requirement for late neural development?

Folic acid or otherwise known as B vitamin (B9) is helps the neural tube to develop. Without folate the neural tube may not close properly. Thus the baby can develop spina bifida. Vitamin's B6 and B12, the minerals Iron and Magnesium, and all the other major and trace minerals and other nutrients which are involved in normal cell division and replication. Including the amino acids, which are the structural building blocks for new tissue.

2. Upload a picture relating to you group project.

[[File:1532-429X-13-20-1.jpg]]

--[[User:Z3330313|z3330313]] 09:37, 18 August 2011 (EST)

--[[User:Z3330313|z3330313]] 12:45, 18 August 2011 (EST) (lab sign in)

== [[LAB4]] ==

'''1. The allantois, identified in the placental cord, is continuous with what anatomical structure? '''

Bladder

'''2. Identify the 3 vascular shunts, and their location, in the embryonic circulation. '''

-Foramen ovale located between atrias and allows direct blood flow between the atria of the embryo without blockage

-Ductus arteriosus located between the pulmonary artery and the ascending aorta.

-Ductus venosus located between the inferior vena cava and the umbilical vein

'''3. Identify the Group project sub-section that you will be researching.'''

-Introduction

-History

-Epidemiology

== [[LAB5]] ==

'''1.Which side (L/R) is most common for diaphragmatic hernia and why?'''

The left side is the most common location for diaphragmatic hernias because it fuses after the right hand side. The failure of the pleuroperitoneal foramen to fuse is the hernia.

--[[User:Z3330313|z3330313]] 02:34, 1 September 2011 (EST)

== [[LAB6]] ==

'''1. What week of development do the palatal shelves fuse?'''

Week 9

'''2. What early animal model helped elucidate the neural crest origin and migration of neural crest cells?'''

Chicken model

'''3. What abnormality results from neural crest not migrating into the cardiac outflow tract?'''

Tetralogy of Fallot

== [[LAB7]] ==

'''1. Are satellite cells (a) necessary for muscle hypertrophy and (b) generally involved in hypertrophy?'''

Satellite cells are not necessary for muscle hypertrophy, however they are involved in the process of development of new muscle fibres.

'''2. Why does chronic low frequency stimulation cause a fast to slow fibre type shift?'''

'''Trisomy 21'''

-Introduction:
Does cover details of the disorder briefly however the format did not flow because for some of the information written it looked as though it belonged to the glossary section of the page. But there was a good use of external links

-Some recent findings:
Regarding the flow of the page the next sub heading did not fit. It would be more appealing if the "some recent findings" heading were to be loacted near the end of the page. However, the information was written very well and easy to read/condensed.

-Trisomy 21 (Down Syndrome) Karyotypes :
The use of images is to be congratulated, it is a helpful visual aid. However, the use of good image was not taken advantage of in written form. The information written was limited and too brief, the writer relied on the image too much.

-Associated Congenital Abnormalities:
This section had a list of the abnormalities however that was just it. There was no explanation of what type of disorder it is or any description what so ever. This section is somewhat of an important sub heading as it deals with abnormal changes to the embryo or fetus during development but the writer only left a brief note which only shows laziness.

-Heart Defect:
Very good use of statistics and external links to help the reader understand the information laid out. Most words were hyperlinked to the glossary section, maybe instead of doing that the writer could just incorpate the information into the main text because it is not just one word but a few thus it would be easier to read it in one go also these words are bulletpointed anyways.

-Limb Defects:
Good use of external links again and a nice image but why not conbine the previous subheading into one heading as, "DEFECTS" because they were both short pieces of information and they both relate to the same topic so it would thus look more appealing and less spaced.

-It would be a suggestion to have a subheading as "epidemiology" so not only information on prevalence will be covered but also statistics on rate of incidence etc.. and why it is occurring at that rate. Furthermore, if Australian statistics were to be used than that would be fantastic as it would be more relevant to us.

-The reference list was good. It was categorised into the different types of sources used. A good job!

--[[User:Z3330313|z3330313]] 00:22, 22 September 2011 (EST)

== [[LAB8]] ==

Hi Mark I forgot to paste the peer reviews on my page last week, so I'm doing it now.

Group 1 - Peer assessment

*Introduction - sentences are too long, especially the first topic sentence however, overall it was quite informative.
*Maybe put in the history to the disease ?
*Epidemiology - the images are not structured properly, it ruins the appearance of the project page. Maybe you could move the first image to the introduction section.
*Etiology - Good use hyperlinks, however again the images are scattered across the page. A structured layout would make reading the information easy to read.
*Clinical Manifestations - Due to the image on the side of the heading I missed the entire heading. It would be a good idea to fix it up. It is nice to see lists because they are easy to read and grabbed information from but there were no explanation paragraphs after the list so it just looks like a compilation of brief information. If there were some information in the form of sentences after the points then it would make this section very informative*.
*Diagnostic Procedures - A suggestion would be to make the sub-headings within the text more prominent because the images in the table make it harder to distinguish the next sub topic. In regards to the table, the use of the images were very good. Maybe you guys could make the images abit smaller though and include another column in the table expanding about the syndrome some more.
*Treatment - Some of the sub-headings have information that are just one sentence long, maybe you guys could just make the whole section into paragraphs instead if you don't choose to expand on the sub topic.
*The glossary looks good but for referencing there is a problem of double, even triple referencing the same paper.

Group 2 - Peer assessment

*The introduction is easy to read and understand. Maybe one thing you could improve on is the organization of the paragraphs because it looks abit too choppy as of now.
*The history looks amazing and well researched AND well referenced! Makes me believe and trust your project even more. Furthermore the picture on the right just makes the section more appealing.
*Epidemiology - the information flows well and examples are also mentioned which is nice to see
*Etiology - The information is ok but maybe it could be better explained with explanation of the technical terms within your texts
*Pathogenesis/Pathophysiology - the student drawn images look amazing! And the organisation of information is good. Maybe a suggestion would be to hyperlink some of the terms in the text because there was alot of technical terms to be scrolling down and up for.
*Diagnostic Tests - The layout is very appealing and consistent with the rest of the page. The spelling of the heading is wrong!
*Maybe for the glossary it would be a good idea to include headings such as "A", "B" etc
*Fixing up double referencing would be a good idea aswell

--z3330313 19:36, 28 September 2011 (EST)

Group 3 - Peer assessment

*The introduction is abit lengthy and choppy because some paragraphs are just 1-2 sentences. Maybe try to connect them into one paragraph and try to make it flow better.
*The history was quite informative maybe put the timeline at the top and the text at the bottom and maybe try to add more recent dates.
*Epidemiology - the use of figures are good and it is explained well in the text
*Aetiology - good idea in external linking images! the information is easy to easy as it is well structured
*Signs and Symptoms - the table is abit confusing to read, althought the information is well reduced
*Other Similar Defects - maybe the use of lines within the table would be better to separate the columns and rows because it is abit hard to read

--z3330313 19:50, 28 September 2011 (EST)

Group 4:

*The page had a nice format that was appealing to read.
*The structuring of the images between and beside the text was perfect because it was not too big and not too small. It was easy to view and nice to see.
*The table for the treatment heading was nice but the last column is hard to read because the information was listed in a horizontal fashion maybe changing it and putting it into dot point form would be good.
*The student drawn image was clear!
*Fixing the formatting/structure of the glossary heading is needed
*Double referencing can be seen
*Sub heading for the video would be nice to see. The idea of including a video is quite nice.

--z3330313 19:57, 28 September 2011 (EST)

Group Project 5

*The introduction was too in detail and did not seem like an introduction. Also there are no references ?
*the history is easy to read
*Etiology - very nice section of information but some sentences seem too long.
*Development of the Disease - was a good idea to put this in and the information is easy to read, maybe include some hyperlinks to the glossary?
*The treatment table is quite informative and easy to read due to its structure and quite appealing to the eyes
*More terms should be added to the glossary

--z3330313 20:02, 28 September 2011 (EST)

Group 6

*The introduction is good but it would be better if there was some referencing.
*The history seemed abit chunky ? maybe a summarised version in a form of a timeline would be good. But overall the use of images is good, it breaks up the heavy text more.
*Epidemiology was abit too short, maybe expanding on why it is this pattern and etc would be a good idea.
*Signs and Symptoms had a nice summary of information. Maybe more pictures would make it more easy on the eyes because this section is quite big on the info. But the audio is a interesting idea!
*Genetics - Firstly, maybe get rid of mark's post. Secondly the layout of information is not that appealing, maybe you could underline the headings to make it more definite. Lastly, the use of images is good! it is very consistent for all genes.
*Diagnostic Tests section was not referenced! If it was then this section would be a winner, if it was completed!
*Overall, it looks like you guys have done alot of research. Good job!

--z3330313 00:01, 29 September 2011 (EST)

Group 7

*The introduction is very brief but it is too the point, maybe add a picture to catch the attention of readers.
*The history had good information but it is not referenced AT ALL. However disregarding the fact that there are no references, the timeline is nice and simple and most importantly easy to understand.
*The epidemiology is short and brief, maybe add a graph to add more information and to show the pattern of the disease. It is nicely referenced
*Aetiology is brief and simple, the image is sized too long thus creating a big gap of space on the page. Either resize the image or fill the space with more information.
*The pathogenesis is quite long and the big image does not help it making the section look more smaller. Maybe cut down and simplify the information.
*Some of the layout needs to be fixed such as the format between the pathogenesis and signs and symptoms.
*Some of the referencing is repeated (double referencing)

--z3330313 00:23, 29 September 2011 (EST)

Group 8

*The introduction had a nice flow, maybe fix the image on the side for better formatting
*A suggestion would be to expand on the timeline because it is quite brief.
*The use of sub-headings do make it easier to read but it looks not appealing because the information after the sub-headings seem too short. Maybe include a graph!
*Aetiology is not referenced well even though there's so much information there.
*Neuropathology section is too long and i wonder is it really needed too this much of an extent.
*Use of tables is good and well written
*The current research section is short and easy to read. It is nice to see that each point is referenced.

--z3330313 00:33, 29 September 2011 (EST)

Group 9

*The introduction is easy to read and brief. It has been referenced well.
*The history section however is difficult to read because there is so much information. Maybe including an image would help and formatting the timeline into a table as well.
*Maybe it would be a good idea to place epidemiology after history for the flow of the page
*And the sub-headings underneath epidemiology deserve its own heading such as treatment and management as it has nothing to do with epidemiology
*Phenotype of Williams Syndrome - nice piece of extra information however it is not referenced at all
*Nothing follows after other problems...
*Other Associated Medical Conditions - so much is dedicated to this section! maybe reduce the amount of info.
*Furthermore the glossary is incomplete
*However overall it is a good start. There were some good images used and the information was understandable

--z3330313 00:57, 29 September 2011 (EST)

Peer Review

*Introduction is way too brief and no referencing what-so-ever
*Combine history and timeline together
*Types of Cleft Palate/Lip was quite an interesting section. Although some of the images were abit too much.
*Double referencing!
*For treatment the layout could have been better, it is hard to read

--z3330313 00:42, 29 September 2011 (EST)

== [[LAB9]] ==

== Red zone - Group 10 project ==

Hi Mark,

I was marked as a red zone student for the group project contributions & discussions.

Concerning the group project contributions:
I may have had a low count of edits because I wrote my parts on word and then uploaded the whole text onto wiki through 1 edit. My contributions to the group are as follows,

''' Duchenne Muscular Dystrophy (DMD)'''
[[File:X_chromosome_location_of_the_dystrophin_gene.jpg|thumb|right|175px|The location of the dystrophin gene on an X chromosome]]
Duchenne muscular dystrophy (DMD) is a sex-linked disorder mostly affecting males because it is a recessive X-linked disease. It is caused by a mutation in the gene that produces the important muscle protein, [[#Glossary of terms|'''dystrophin''']]. In humans this [[#Glossary of terms|'''gene''']] is located on the [[#Glossary of terms|'''X chromosome''']], thus if a female has one affected X-chromosome then they are said to be a carrier of the disorder and can pass on the altered gene to her offspring. However, if a male inherits the altered X-chromosome they will become a sufferer of this disease because they only have one X-chromosome.

The dystrophin gene is the largest gene in nature on locus Xp21, spanning 1.5% of the X-chromosome which may explain it’s unusually high spontaneous mutation rate <ref>(http://hstalks.com.wwwproxy0.library.unsw.edu.au/main/citation_info.php?c=252)</ref>. In DMD the protein dystrophin is not produced, when it is an important structural component for muscle tissue during contraction. Thus it results in muscle degeneration, difficulty in walking, breathing and death. The increase in muscle damage accompanies abnormal blood flow within the muscle which leads to progressive limb weakness, respiratory and cardiac failure and eventually premature death <ref><pubmed>21574524</pubmed></ref>.
The rate of progression of the disorder is fast and the age of onset is from 2-6yrs of age.<ref>(http://dystrophy.com/muscular-dystrophy/Types+of+Muscular+Dystrophies)</ref>.

Pathologically, the main feature found in muscle biopsies from patients that suffer from DMD is [[#Glossary of terms|'''fibrosis''']] <ref><pubmed>20613637</pubmed></ref>, the muscle is replaced with fibro-adipose tissue and it directly causes muscle dysfunction and contributes to the lethal DMD [[#Glossary of terms|'''phenotype''']] <ref><pubmed>21263136</pubmed></ref>. Unfortunately there is no known cure for this disorder, however due to advances in this technological era there are now many treatment methods that help delay the progress of the disease and manage the symptoms associated with it. Patients of DMD experience poor life quality and an extremely lowered life expectancy, it was only until recently, procedures that delayed the progress of the disease and that help increase the quality of life have been brought about <ref><pubmed>19774532</pubmed></ref>.

'''History'''

'''Historical Background of DMD'''

{|border="1"
|-style="background:cadetblue" align="center"
|'''Date'''
|'''Brief description'''
|-style="background:"
|1847
|
Dr W J Little reported two affect boys aged 12 & 14 that were unable to walk. Both were later found to have most of their leg muscles replaced with fat <ref name="PMID8326496"><pubmed>8326496</pubmed></ref>.

|-style="background:"
| 1851
|
Meryon described at a meeting of the Royal Medical and Chirurgical Society 8 boys presumed to be affected with Duchenne Muscular Dystrophy <ref name="PMID8326496"/>

|-style="background:"
| 1861
|
Duchenne first describes the disease, a young boy whose condition characterised by the hypertrophy of the boy's calf muscles <ref name="PMID16225184"/>

|-style="background:"
| 1868
|
Duchenne provided a much more detailed account of the boy's disease, DMD <ref name="PMID16225184"/>

|-style="background:"
| 1930-1960
|
Discovery of Becker Muscular Dystrophy, a less severe form form of DMD. The x-linked pattern of inheritance for DMD is confirmed.<ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)">MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)</ref>.

|-style="background:"
|1985-1988
|
Gene responsible for DMD is found by Louis Kunkel's team & the protein made from this gene is described and named dystrophin <ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)"/>

|-style="background:"
|1989-1994
|
The reason for severity of DMD is found. It is determined by the amount of dystrophin present in the muscle-fibre membrane. The less dystrophin the more severe the symptoms <ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)"/>

|-style="background:"
|1995-2000
|
Dystrophin gene is miniturised to facilitate gene therapy and research into stem cells is on its way to cure DMD <ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)"/>.

|-style="background:"
|2001-2005
|
Corticosteroid prednisone trials found effective in slowing down the progression of DMD <ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)"/>.

|-style="background:"
|2005-present
|
Important research on the autosomal homologue of dystrophin, ''utrophin''. It is found to have a strong ameliorating effect on the pathogenesis of DMD and has extreme potential for being effective treatment for all genetic mutations of Duchenne and Becker's muscular dystrophy.

|}

'''Dr Edward Meryon'''

Throughout history there have been cases that suggested muscular dystrophy, however, the first clinical descriptions of dystrophy in the English language did not appear until the 19th century. <ref>Alan E. H. Emery, 1987, Duchenne Muscular dystrophy, Oxford Medical Publications, New York. pp.10</ref>. The earliest report of muscular dystrophy was from Dr Edward Meryon of St. Thomas’s Hospital, London. Born in 1809, Meryon was an English physician. He published several books concerning the nervous system and in one of his publications Meryon described eight affected boys in three families with a disease later to be identified as Duchenne Muscular Dystrophy<ref name="PMID8326496"><pubmed>8326496</pubmed></ref>. His findings were reported in the Transactions of the Medical and Chirurgical Society in December 1851 <ref name="Alan E. H. Emery, 1987, Duchenne Muscular dystrophy, Oxford Medical Publications, New York. pp.12">Alan E. H. Emery, 1987, Duchenne Muscular dystrophy, Oxford Medical Publications, New York. pp.12</ref>.

In his studies of the disease, Meryon conducted several necropsies and found the spinal cords were intact which concluded that the disease was not from the nervous system. Instead, he found that the muscles throughout the body were atrophied, soft and almost bloodless. Further microscopic examination of the muscle showed that the muscular fibres were broken down and converted into granular, fatty matter <ref name="PMID8326496"/>. Therefore Meryon named the condition “Granular degeneration of the Voluntary muscle”. Meryon concluded there was a familiar nature to the disease that was selective for males which primarily affected muscle tissue <ref name="Alan E. H. Emery, 1987, Duchenne Muscular dystrophy, Oxford Medical Publications, New York. pp.12"/>.

Out of the three families he studied there were eight affected brothers and nine healthy sisters, this supported his conclusion of the disease being selective to males. Meryon’s discovery was of 10 years prior to Duchenne. He characterised the disorder as a progressive muscle wasting disease leading to premature death in the late teens, that begins in early childhood. The disease was later to be referred to as Duchenne muscular dystrophy.

[[File:Duchenne.JPG| right| 200px| Guillaume Benjamin Amand Duchenne | thumb]]
'''Guillaume Benjamin Amand Duchenne'''

Guillaume Benjamin Amand Duchenne was the first to describe DMD, and thus the disease is named after him. He was born in Boulogne-sur-Mer in France, on 17 September 1806 <ref name="PMID16225184"><pubmed>16225184</pubmed></ref>. Duchenne was a family doctor for 11 years who was interested in the study of electrical stimulation of muscle <ref name="PMID16225184"/>. He first became interested in muscular dystrophy in 1858, and formally described it in 1861. Duchenne also invented the “harpoon” which was a needle system that he utilised to obtain percutaneous samples of muscular tissue without anesthesia <ref name="PMID16225184"/>. This technique allowed study of material from the same patient at different stages of the disease.

Duchenne defined the disorder as:
* progressive weakness of movement first affecting the lower limb then later the upper

* pathologically; loss of striation of muscle replaced by granular matter and fat vesicles. Furthermore an increase in interstitial connective tissue in affected muscles with the production of abundant fibrous and adipose tissue in the later stages

* a gradual increase in the size of many affected muscles

* an onset during early childhood or early adolescence that is, more prevalent in boys than girls

* can affect several children in a family <ref><pubmed>10449553</pubmed></ref>

'''Epidemiology'''

{| align="left" style="border: solid 1px #a0a0ff"
|- align="left" style="background:#8eb2ec"
|-style="background:cadetblue" align="left"
|'''State'''
|'''Incident rate (per 100 000 Male-liveborns)'''
|-style="background:"
| Western Australia
|
20.2 <ref name="PMID7205898"><pubmed>7205898</pubmed></ref>

|-style="background:"
| Victoria
|
21.9 <ref name="PMID7205898"/>

|-style="background:"
| Queensland
|
16.4 <ref name="PMID7205898"/>

|-style="background:"
| NSW & ACT
|
18.6 <ref name="PMID7205898"/>

|}

The incidence rate for DMD is about 1 in 3500 boys. All ethnic groups are equally affected. The most common form of muscular dystrophy found in children is Duchennes and it predominately affects males because it is an X-linked recessive disorder. Interestingly the average age of diagnosis is 5 despite the earlier onset of symptoms <ref><pubmed> 19834452</pubmed></ref>. Between 1960 to 1971, one per 5377 liveborn males or one per 5226 liveborn males surviving to five years of age had Duchenne muscular dystrophy. Of these 64% were isolated cases meaning they were the only affected member of the family and 34% were familiar cases in New South Wales and the ACT <ref><pubmed> 7205898 </pubmed></ref>.

My work is still under work.

And also regarding my discussions, most of the time I spoke to the members through face to face talks because I see the group 10 members during the week in my other classes. We also contact eachother through text message and facebook etc.

--[[User:Z3330313|z3330313]] 02:15, 10 October 2011 (EST)

==Lab 10 Online Assessment==
# Besides fetal alcohol syndrome, identify another environmental teratogen that can lead to hearing loss.

-Rubella virus

# Identify 3 factors that contribute to poor neonatal drainage of the middle ear.

The auditory tube's angle is almost horizontal, it is also short and narrow.

# Identify 1 genetic abnormality that affects hearing development and link to the OMIM record. (Your individual abnormality should be different from all other students)

Treacher Collins syndrome

http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Treacher_Collins_syndrome?open

==Lab 11 Online Assessment==

1. Name the components that give rise to the interatrial septum and the passages that connect the right and left atria.

The two components that give rise to the interatrial septum are the septum primum and the septum secundum. During the passage that connects the right and left atria are open and those two passages are foramen ovale and foramen secundum.

2. Identify the cardiac defects that arise through abnormal development of the outflow tract

-pulmonary stenosis
-aortic stenosis

==Lab 12 Online Assessment==

1. Give examples of 3 systems that continue to develop postnatally.

-respiratory system
-gastrointestinal system
-reproductive system

2. Identify the abnormalities detected by the Guthrie Test and link to one abnormality listed in OMIM.

-Cystic Fibrosis
-Homocystinuria
-Galactosemia

--[[User:Z3330313|Joanna Pak]] 18:09, 28 October 2011 (EST)

2011-10-08T03:15:07Z

Z3330313: /* History */

----

{{2011Projects}}

== Duchenne Muscular Dystrophy (DMD) ==
[[File:X_chromosome_location_of_the_dystrophin_gene.jpg|thumb|right|175px|The location of the dystrophin gene on an X chromosome]]
Duchenne muscular dystrophy (DMD) is a sex-linked disorder mostly affecting males because it is a recessive X-linked disease. It is caused by a mutation in the gene that produces the important muscle protein, [[#Glossary of terms|'''dystrophin''']]. In humans this [[#Glossary of terms|'''gene''']] is located on the [[#Glossary of terms|'''X chromosome''']], thus if a female has one affected X-chromosome then they are said to be a carrier of the disorder and can pass on the altered gene to her offspring. However, if a male inherits the altered X-chromosome they will become a sufferer of this disease because they only have one X-chromosome.

The dystrophin gene is the largest gene in nature on locus Xp21, spanning 1.5% of the X-chromosome which may explain it’s unusually high spontaneous mutation rate <ref>(http://hstalks.com.wwwproxy0.library.unsw.edu.au/main/citation_info.php?c=252)</ref>. In DMD the protein dystrophin is not produced, when it is an important structural component for muscle tissue during contraction. Thus it results in muscle degeneration, difficulty in walking, breathing and death. The increase in muscle damage accompanies abnormal blood flow within the muscle which leads to progressive limb weakness, respiratory and cardiac failure and eventually premature death <ref><pubmed>21574524</pubmed></ref>.
The rate of progression of the disorder is fast and the age of onset is from 2-6yrs of age.<ref>(http://dystrophy.com/muscular-dystrophy/Types+of+Muscular+Dystrophies)</ref>.

Pathologically, the main feature found in muscle biopsies from patients that suffer from DMD is [[#Glossary of terms|'''fibrosis''']] <ref><pubmed>20613637</pubmed></ref>, the muscle is replaced with fibro-adipose tissue and it directly causes muscle dysfunction and contributes to the lethal DMD [[#Glossary of terms|'''phenotype''']] <ref><pubmed>21263136</pubmed></ref>. Unfortunately there is no known cure for this disorder, however due to advances in this technological era there are now many treatment methods that help delay the progress of the disease and manage the symptoms associated with it. Patients of DMD experience poor life quality and an extremely lowered life expectancy, it was only until recently, procedures that delayed the progress of the disease and that help increase the quality of life have been brought about <ref><pubmed>19774532</pubmed></ref>.

== History ==

'''Dr Edward Meryon'''

Throughout history there have been cases that suggested muscular dystrophy, however, the first clinical descriptions of dystrophy in the English language did not appear until the 19th century. <ref>Alan E. H. Emery, 1987, Duchenne Muscular dystrophy, Oxford Medical Publications, New York. pp.10</ref>. The earliest report of muscular dystrophy was from Dr Edward Meryon of St. Thomas’s Hospital, London. Born in 1809, Meryon was an English physician. He published several books concerning the nervous system and in one of his publications Meryon described eight affected boys in three families with a disease later to be identified as Duchenne Muscular Dystrophy<ref name="PMID8326496"><pubmed>8326496</pubmed></ref>. His findings were reported in the Transactions of the Medical and Chirurgical Society in December 1851 <ref name="Alan E. H. Emery, 1987, Duchenne Muscular dystrophy, Oxford Medical Publications, New York. pp.12">Alan E. H. Emery, 1987, Duchenne Muscular dystrophy, Oxford Medical Publications, New York. pp.12</ref>.

In his studies of the disease, Meryon conducted several necropsies and found the spinal cords were intact which concluded that the disease was not from the nervous system. Instead, he found that the muscles throughout the body were atrophied, soft and almost bloodless. Further microscopic examination of the muscle showed that the muscular fibres were broken down and converted into granular, fatty matter <ref name="PMID8326496"/>. Therefore Meryon named the condition “Granular degeneration of the Voluntary muscle”. Meryon concluded there was a familiar nature to the disease that was selective for males which primarily affected muscle tissue <ref name="Alan E. H. Emery, 1987, Duchenne Muscular dystrophy, Oxford Medical Publications, New York. pp.12"/>.

Out of the three families he studied there were eight affected brothers and nine healthy sisters, this supported his conclusion of the disease being selective to males. Meryon’s discovery was of 10 years prior to Duchenne. He characterised the disorder as a progressive muscle wasting disease leading to premature death in the late teens, that begins in early childhood. The disease was later to be referred to as Duchenne muscular dystrophy.

'''Guillaume Benjamin Amand Duchenne'''

[[File:Duchenne.JPG| right| 200px| Guillaume Benjamin Amand Duchenne | thumb]]

Guillaume Benjamin Amand Duchenne was the first to describe DMD, and thus the disease is named after him. He was born in Boulogne-sur-Mer in France, on 17 September 1806 <ref name="PMID16225184"><pubmed>16225184</pubmed></ref>. Duchenne was a family doctor for 11 years who was interested in the study of electrical stimulation of muscle <ref name="PMID16225184"/>. He first became interested in muscular dystrophy in 1858, and formally described it in 1861. Duchenne also invented the “harpoon” which was a needle system that he utilised to obtain percutaneous samples of muscular tissue without anesthesia <ref name="PMID16225184"/>. This technique allowed study of material from the same patient at different stages of the disease.

Duchenne defined the disorder as:
* progressive weakness of movement first affecting the lower limb then later the upper

* pathologically; loss of striation of muscle replaced by granular matter and fat vesicles. Furthermore an increase in interstitial connective tissue in affected muscles with the production of abundant fibrous and adipose tissue in the later stages

* a gradual increase in the size of many affected muscles

* an onset during early childhood or early adolescence that is, more prevalent in boys than girls

* can affect several children in a family <ref><pubmed>10449553</pubmed></ref>

'''Brief Timeline of DMD'''

{|border="1"
|-style="background:cadetblue" align="center"
|'''Date'''
|'''Brief description'''
|-style="background:"
|1847
|
Dr W J Little reported two affect boys aged 12 & 14 that were unable to walk. Both were later found to have most of their leg muscles replaced with fat <ref name="PMID8326496"><pubmed>8326496</pubmed></ref>.

|-style="background:"
| 1851
|
Meryon described at a meeting of the Royal Medical and Chirurgical society 8 boys presumed to be affected with Duchenne Muscular Dystrophy <ref name="PMID8326496"/>

|-style="background:"
| 1861
|
Duchenne first describes the disease, a young boy whose condition characterised by the hypertrophy of the boy's calf muscles <ref name="PMID16225184"/>

|-style="background:"
| 1868
|
Duchenne provided a much more detailed account of the boy's disease,DMD <ref name="PMID16225184"/>

|-style="background:"
| 1868
|
Duchenne provided a much more detailed account of the boy's disease,DMD <ref name="PMID16225184"/>

|-style="background:"
| 1930-1960
|
Discovery of Becker Muscular Dystrophy, a less severe form form of DMD. The x-linked pattern of inheritance for DMD is confirmed.<ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)">MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)</ref>.

|-style="background:"
|1985-1988
|
Gene responsible for DMD is found by Louis Kunkel's team & the protein made from this gene is described and named dystrophin <ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)"/>

|-style="background:"
|1989-1994
|
The reason for severity of DMD is found. It is determined by the amount of dystrophin present in the muscle-fibre membrane. The more dystrophin correlates to less severe symptoms <ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)"/>

|-style="background:"
|1995-2000
|
Dystrophin gene is miniturised to facilitate gene therapy and research into stem cells is on its way to cure DMD <ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)"/>.

|-style="background:"
|2001-2005
|
Corticosteroid prednisone trials found effective in slowing down the progression of DMD <ref name="MDA 2011, Milestones in Duchenne Muscular Dystrophy Research, (http://www.mdausa.org/publications/milestones-embed.html)"/>.

|}

== Epidemiology ==

{| align="left" style="border: solid 1px #a0a0ff"
|- align="left" style="background:#8eb2ec"
|-style="background:cadetblue" align="left"
|'''State'''
|'''Incident rate (per 100 000 Male-liveborns)'''
|-style="background:"
| Western Australia
|
20.2 <ref name="PMID7205898"><pubmed>7205898</pubmed></ref>

|-style="background:"
| Victoria
|
21.9 <ref name="PMID7205898"/>

|-style="background:"
| Queensland
|
16.4 <ref name="PMID7205898"/>

|-style="background:"
| NSW & ACT
|
18.6 <ref name="PMID7205898"/>

|}

The incidence rate for DMD is about 1 in 3500 boys. All ethnic groups are equally affected. The most common form of muscular dystrophy found in children is Duchennes and it predominately affects males because it is an X-linked recessive disorder. Interestingly the average age of diagnosis is 5 despite the earlier onset of symptoms <ref><pubmed> 19834452</pubmed></ref>. Between 1960 to 1971, one per 5377 liveborn males or one per 5226 liveborn males surviving to five years of age had Duchenne muscular dystrophy. Of these 64% were isolated cases meaning they were the only affected member of the family and 34% were familiar cases in New South Wales and the ACT <ref><pubmed> 7205898 </pubmed></ref>.

A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome. Males only have one X chromosome and therefore, one altered or mutated copy of the gene is capable of causing the condition. Because of the X-linked nature of this disease in terms of its inheritance, males are more likely to develop symptoms characteristic to this disease than females. There is a high 50% chance of sons of female carriers to have the disease, with daughters having alternatively, a 50% chance of being a carrier. <ref> Medline Plus (August, 2011). “Duchenne muscular dystrophy”. Accessed via: http://www.nlm.nih.gov/medlineplus/ency/article/000705.htm</ref> A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Although Duchenne Muscular Dystrophy is regarded as an X-linked recessive disorder, if often still occurs in individuals without a known family history through ''de novo'' mutations.<ref>U.S. National Library of Medicine (2011). “Genes: DMD”. Author unknown, Genetics Home Reference. Accessed via http://ghr.nlm.nih.gov/gene/DMD.</ref>

''(I have a figure in mind but I can't find the copyright information on its' page, I will be asking Mark tomorrow about it)''--[[User:Z3330313|z3330313]] 21:39, 5 October 2011 (EST)

== Aetiology - Genetics ==
[[File:Dystrophin_in_the_muscle_fibre_membrane.jpg|thumb|right|250px|Dystrophin as found in the muscle fibre membrane]]

The largest gene of the human [[#Glossary of terms|'''genome''']] is called the [[#Glossary of terms|'''dystrophin''']] [[#Glossary of terms|'''gene''']] and is contained at the [[#Glossary of terms|'''sacroplasmic''']] surface of the plasma membrane or [[#Glossary of terms|'''sarcolemma''']] of muscle fibers.<ref name=Davies>Davies.K.E, Nowak. K.J (2006). "Molecular mechanisms of musclar dystrophies: old and new players." Nature Reviews. October, 2006 Volume 7, pages 763-773.</ref> This particular gene codes for the dystrophin protein which plays a very important role in the structural stability of [[#Glossary of terms|'''muscle fibres''']].

The dystrophin gene, also known as DMD, is located on the short arm of the [[#Glossary of terms|'''X chromosome''']] at position 21.2. In 1987, it was found that this particular gene was identified as being located from [[#Glossary of terms|'''base pair''']] 31,137,344 to base pair 33,357,725 on the X chromosome. <ref name=DMD>Genetics Home Reference. 2011. “Genes: DMD” Author anonymous. Accessed via. http://ghr.nlm.nih.gov/gene/DMD</ref> <ref name=Davies/> In its normal functional form, this gene produces the protein dystrophin that has multiple forms, but however is found mostly commonly in skeletal and cardiac muscles. <ref name=DMD/>

The exact function of dystrophin has not yet been well defined, however it is suggested that dystrophin plays an important structural, protective role and signalling role during [[#Glossary of terms|'''muscle contraction''']].

The following table summaries the 3 main roles of dystrophin in muscle fibres.

{|border="1"
|-style="background:cadetblue" align="center"
|'''Role of dystrophin'''
|'''Brief description'''
|-style="background:"
| Structural role
|
*Dystrophin is expressed within the sacrolemma and secures the sarcolemma to the [[#Glossary of terms|'''actin''']] [[#Glossary of terms|'''cytoplasm''']]
*This protein is said to be enriched in areas of cell-to-cell contact and is thought to be elastic and flexible hence protecting muscles from stress during contraction. <ref name=Davies/>

|-style="background:"
| Protective role
|
*One end of dystrophin binds to the [[#Glossary of terms|'''cytoskeleton''']] through [[#Glossary of terms|'''filamentous''']] actin whilst the other binds to the [[#Glossary of terms|'''dystrophin-associated protein complex (DAPC)''']].
*The DAPC consists of cytoplasmic, [[#Glossary of terms|'''transmembrane''']] and extracellular proteins that provide a strong mechanical link between the intracellular cytoskeleton and the [[#Glossary of terms|'''extracellular matrix''']].
*In the absence of dystrophin, the DAPC weakens due to the loss of sarcolemmal integrity, resulting in muscle fibres being more susceptible to damage.<ref name=Davies/>

|-style="background:"
| Signalling role
| There are numerous examples that suggest a role of dystrophin in cell signalling. One example that will be given is the signalling role of alpha- syntrophin.
*Syntrophin links to the extracellular matrix through dystrophin and creates signal transduction complexes at the DAPC.
*Studies on mice show that in the absence of dystrophin, alpha-syntrophin is almost completely lost from the sarcolemma. This suggests that dystrophin plays an intermediate role in cell signalling pathways and especially in connecting signalling proteins to the DAPC.<ref name=Davies/>

|}

[[File:Point_mutations_resulting_in_DMD.jpg|350px|thumb|right|Point mutations that result in the occurance of Becker and Duchenne Muscular Dystrophy]]

Generally, muscular dystrophies can be inherited as [[#Glossary of terms|'''dominant''']] or [[#Glossary of terms|'''recessive''']] traits, or can be due to new mutations of a specific gene. <ref name=Davies/>As the dystrophin gene is located on the X chromosome, it can be said to be an inherited X-linked recessive condition. In the majority of affected males, the mutated gene has been inherited from the mother who is a carrier of an altered dystrophin gene, whilst a smaller minority of male cases are the result from a new mutation of this gene. In females, as they have two X chromosomes if one altered gene is expressed they are classified as carriers in that they ‘carry’ the altered gene but do not encounter any of the signs or symptoms of DMD. <ref>Genetics Home Reference. 2011. “Genetic Conditions: Duchenne and Becker muscular dystrophy.” Author anonymous. Accessed via. http://ghr.nlm.nih.gov/condition/duchenne-and-becker-muscular-dystrophy</ref>

Mutations in the DMD gene can often result in the abnormal production or function of the protein, dystrophin. Some of these mutations include the deletion of part of the gene, abnormal duplication or alterations in the number of nucleotides. The two most common forms of muscular dystrophy are: Duchenne and Beckers Muscular Dystrophy.

The image based on point mutations is a visual display of the different types of mutations of the dystrophin gene that result in different forms of musuclar dystrophy. The first reading frame is that of a normal dystrophin gene and can be compared to the second reading frame that reflects a point mutation in which one of the bases has been altered, resulting in an abnormal production of dystrophin. This type of mutation results in what is clinically known as Becker’s Muscular Dystrophy (BMD). The second reading frame can then be further compared to the final reading frame that has a point deletion mutation, resulting in a new reading frame for this particular gene. The end result is a truncated protein product that is known as Duchenne Muscular Dystrophy (DMD). <ref>Medscape Reference (2011). Dystrophinopathies. Site author: Michelle L Mellion. Accessed via: http://emedicine.medscape.com/article/1173204-overview#a0104 </ref>

== Pathogenesis ==

[[File:Normal control muscle (a) vs. Duchennes muscular dystrophy muscle (b).jpg|200px|thumb|right|"Myofibers of normal control muscles(a)and Duchenne muscular dystrophy muscle (DMD)(b)"]]

Dystrophin is needed in all muscle cells of the body - this includes skeletal muscles, smooth muscle and cardiac muscle. The exact function of dystrophin is unknown - it is thought to secure the [[#Glossary of terms|'''sarcolemma''']] to the actin [[#Glossary of terms| '''cytoskeleton''']] of the muscle cell. This adds strength and rigidity, protecting the muscle when it contracts<ref name= Chamberlain>Chamberlain, J. (2007),''' "Duchenne Muscular Dystrophy"''', in Dunn, B. (ed.), Protein Epidemiology: Diseases at the Level of Protein Structure and Function, The Biomedical & Life Sciences Collection, London (online at http://hstalks.com/bio).</ref>.

In Duchenne Muscular Dystrophy, a mutation on the dystrophin gene causes a lack or absence of dystrophin, which causes many problems. Without dystrophin, the muscle cells can be easily damaged during contraction- the cell membrane becomes very permeable and allows extracellular material in. This causes swelling, until the pressure causes it to burst. Muscle fibres can also split, or begin a detrimental cycle of repeated [[#Glossary of terms |'''necrosis''']] and regeneration.<ref>S Carpenter, G Karpati. '''Duchenne Muscular Dystrophy: Plasma Membrane Loss Initiates Muscle Cell Necrosis Unless it is Repaired.''' Brain: 1979, 102(1): 147-161 doi:10.1093/brain/102.1.147.</ref> Necrosis often occurs in zones within the muscle fibres, a characteristic feature of Duchenne disease. The rate at which necrosis occurs is faster than the rate at which the tissue can regenerate, so the muscle fibres progressively disappear. <ref>Sarnat, H.B. (1983) '''Muscle Pathology and Histochemistry''', American Society of Clinical Pathologists, USA: 114.</ref>.

Within the extracellular material are calcium ions, which cause serious damage when there is an influx into the muscle. Calcium activates the enzyme [[#Glossary of terms| '''protease''']], an enzyme that breaks down proteins and peptides. In the muscle, this results in necrosis of [[#Glossary of terms| '''myocytes''']] and inflammation.<ref name="Spurney">Spurney, C. F. (2011), Cardiomyopathy of duchenne muscular dystrophy: Current understanding and future directions. Muscle & Nerve, 44: 8–19. doi: 10.1002/mus.22097</ref> In the heart, increased intracellular calcium activates another protease called calpain, which deteriorates the contractile muscle<ref name="Spurney"/>. This increases the stress placed on the remaining functional heart muscle.

A key part of the pathogenesis is the replacement of dead muscle fibres with connective tissue (fibrosis) and adipose tissue<ref name=Chamberlain/>. Although components of connective tissue, such as collagen, have high tensile strength, it does not and cannot function like muscle. Significant amounts of fibroid material weaken and hinder normal muscle contraction. In the heart, this is known as cardiomyopathy, and causes serious complications for sufferers of DMD.

The picture on the right is a comparison of normal muscle tissue with DMD muscle tissue. Note the absent muscle cells, the fibrous material in between the myocytes in (b) and (c), and the lack of uniformity and rigidity. These features are characteristic of DMD.

== Clinical Manifestations & Complications ==
[[Image:Symptoms of DMD.JPG|300px|thumb|right|Symptoms of DMD]]
====Signs and Symptoms of Duchenne Muscular Dystrophy====

Many of the symptoms associated with DMD are due to the instability and weakness of the body's skeletal muscles. In particular, those symptoms associated with movement such as running, jumping, keeping balance and raising oneself from the ground are particularly prominent. However, he general signs and symptoms of DMD are not usually apparent until the child is 3 years old<ref>Bupa(2009). “Duchenne muscular dystrophy”. Accessed via: http://www.bupa.co.uk/individuals/health-information/directory/d/duchenne-muscular-dystrophy</ref>, or when major milestones such as learning to walk, are missed or delayed. Other complications, such as curvature of the spine or respiratory impairment are symptoms that often arise secondarily, or at a later stage in the progression of the disease. These manifestations and complications are elaborated further below.

Some typical symptoms include:
* Delayed motor movements<ref name=Medscape>http://emedicine.medscape.com/article/1173204-clinical</ref>
* Frequent falls and poor balance<ref name=Nelson>Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Muscular dystrophies. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa:Saunders Elsevier; 2007:chap 608.</ref>
* Weak skeletal muscles - causes difficulty running, jumping, and getting up from a sitting or lying down position<ref name=Nelson/>
* Large calf muscles (pseudohypertrophy) <ref name=Nelson/>
* Walking on toes or waddling gait<ref name=Medscape/>
* Abnormal curvature of the spine<ref name=Bushby>Bushby, K., Bourke, J., Bullock, R., Eagle, M., Gibson, M. & Quinby, J. (2005) The multidisciplinary management of Duchenne muscular dystrophy. Current Paediatrics, 15, 292-300</ref>
* Cardiac, respiratory and cognitive impairment<ref name=Nelson/>

====Skeletal muscle====
[[File:Gower's sign - a symptom of DMD.JPG|300px|thumb|right|Gower's sign]]
[[File:Spinal_problems_DMD.jpg|300px|thumb|right|Spinal deformity in DMD]]
The degeneration of skeletal muscle causes many problems with mobility. In early childhood, a child affected with DMD may take longer than other children to sit or begin standing and walking. Young children may develop a waddling gait, a characteristic feature of DMD.<ref name =Medscape/> As the disease progresses, walking (especially up stairs) can become extremely difficult, and many children are confined to a wheelchair by between the ages of 8 and 11.<ref name=Chamberlain/> Other indicators of the disease include [[#Glossary of terms| '''pseudohypertrophy''']] (particularly of the calf muscles), fatigue, leg cramps and Gower's Sign<ref>http://books.google.com.au/books?id=HEUZnAd4L98C&printsec=frontcover&dq=duchenne+muscular+dystrophy&hl=en&ei=xiRkTsC5B-vzmAXx8r2sCg&sa=X&oi=book_result&ct=result&resnum=1&ved=0CCsQ6AEwAA#v=onepage&q&f=false</ref>. Gower's Sign is particularly characteristic of DMD - it is where the child, from a kneeling position, will push their arms up along their legs to help them stand.
A person with DMD may also suffer from [[#Glossary of terms|'''joint contractures''']] in the ankle, knees and hips<ref>Stone, K., Tester, C., Howarth, A., Blakeney, J., Traynor, N., McAndrew, H., McCutcheon, M.(2007)'''Occupational Therapy and Duchenne Muscular Dystrophy'''. John Wiley & Sons, England.</ref>

In addition to effects on body movement, DMD can cause problems with the spine. If the muscles around the spine (such as latissimus dorsi, erector spinae and trapezius muscles) weaken or [[#Glossary of terms| '''atrophy''']], [[#Glossary of terms| '''scoliosis''']] can develop. As high as 90% of people affected by DMD will develop clinically significant scoliosis. <ref name= Bushby/> If the muscles degenerate unevenly, kyphosis<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002220/</ref> can occur - excessive ''outward'' curvature of the thoracic spine (resulting in a hunched or rounded back), or lordosis<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0003762/</ref> - excessive ''inward'' curvature of the lumbar spine (resulting in a pushed forward abdomen and backwards extending hips).

====Cardiac muscle====
A very common and serious complication of DMD is [[#Glossary of terms| '''cardiomyopathy''']]- on average, 20% of DMD sufferers will die from cardiac failure.<ref name=Chamberlain/> Cardiac muscle is affected in a similar way to skeletal muscle, in which the sarcolemma loses integrity and necrotic tissue is replaced by fat and connective tissue. This severely compromises the strength and ability of the heart to contract properly and circulate blood around the body. If the heart cannot pump blood properly, cells will not receive enough oxygen for normal function. The area of the heart that is most affected is the lateral postero-basal side of the left ventricle, as this area takes the greatest strain as the heart beats<ref name = Bushby/>. Currently, there is no evidence to suggest that DMD affects the conduction system of the heart, however <ref>Bushby K, Muntoni F, Bourke JP. '''107th ENMC international workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy'''. 7th-9th June 2002, Naarden, the Netherlands. Neuromuscul Disord 2003; 13:166-172</ref><ref>Finsterer J, Stollberger C.''' The heart in human dystrophinopathies'''. Cardiology 2003; 99:1-19.</ref>, in the late stages of the disease, the large quantities of fibroid material in the heart can cause [[#Glossary of terms| '''systolic''']] dysfunction and ventricular [[#Glossary of terms|'''arrhythmias''']].

====Smooth muscle====
DMD in the gastrointestinal tract means the muscles cannot contract properly (peristalsis), resulting in constipation or diarrhoea. Muscles in the oesophagus can weaken, and cause difficulties swallowing food (leading to under-nutrition), [[#Glossary of terms| '''pulmonary aspiration''']], heartburn from reflux of gastric acid<ref><pubmed>7037523</pubmed></ref>. Some may have delayed gastric emptying and sphincter dysfunction.<ref name=Smuscle><pubmed>PMID3380114</pubmed></ref> The stomach may lose its strength, or in the most extreme cases, patients may also suffer from [[#Glossary of terms |'''acute gastric dilation''']] or intestinal [[#Glossary of terms|'''pseudo-obstruction''']], both of which can be fatal.<ref name=Smuscle/>

====Respiratory problems====
Problems relating to respiratory function become most prevalent when the person requires a wheelchair or assistance in moving. By this stage of the disease, overall muscle strength is low, especially muscles such as the diaphragm and other muscles associated with breathing. The person may have difficulties breathing, or may not be able to inspire or expire to their maximum capacity. They may not be able to cough properly either.<ref name= MDFAus>http://mdaustralia.org.au/files/2011/07/002_duchenne_becker-2011.pdf.</ref> As the lungs cannot function wholly, gas exchange is compromised. From this, [[#Glossary of terms|'''hypercapnia''']] may develop and can affect energy levels, weight management, cause bad headaches and disturb sleep.<ref name=Bushby/>Combined, these symptoms increase susceptibility or predispose the patient to a range of pulmonary infections, such as pneumonia. Approximately 80% of Duchenne sufferers will die from respiratory failure or a related illness.<ref name=Chamberlain/>

The degree of muscle strength may be (indirectly) measured by a Forced Vital Capacity (FVC) - the volume of air that can be forcibly expelled after a full inspiration. If the FVC is low, this is indicative of poor muscle strength and therefore possible respiratory failure.<ref name=Bushby/>

====Cognitive Impairment====
In the central nervous system (CNS), dystrophin is found:
*on the [[#Glossary of terms|'''soma''']] and [[#Glossary of terms|'''proximal''']] [[#Glossary of terms|'''dendrites''']] of pyramidal cells in the [[#Glossary of terms|'''cerebral cortex''']] and [[#Glossary of terms|'''hippocampus''']].<ref name =Poysky><pubmed>17720499</pubmed></ref> Pyramidal cells are implicated in cognitive ability and play a role in vision-guided motor movement.<ref><pubmed>18632946</pubmed></ref>
*in Purkinje cells in the cerebellum<ref name= Poysky/> - Purkinje cells are large inhibitory neurons in the cortex of the cerebellum. Their main function is in controlling motor movement.<ref>Rose, S. (2005) The future of the brain: the promise and perils of tomorrow's neuroscience. Oxford University Press: Oxford, England.</ref>

The ''exact'' role of dystrophin in brain function is not known as research in this field is still in its infancy. From what has been found so far, it is believed that it affects the electrophysiology of neurons, calcium homeostasis and synaptic plasticity.<ref name= Poysky/> In particular reference to the locations above, an absence of dystrophin causes a disruption in normal brain function.

The Muscular Dystrophy Association of Australia reports that up to one third of boys will suffer from a mental disability associated with DMD. <ref name=MDFAus/><ref name=Chamberlain/> However, very few are ‘severely’ impaired. Difficulties mostly arise in terms of emotional and social interaction – more specifically, in behavioural and communication skills. In a study of 1224 DMD patients and intelligence, it was found the average IQ was lower by one standard deviation than the normal population, and 35% of the boys had IQ scores in the mental retardation range (<70).<ref name=Cotton/> In particular, verbal skills are predominately affected, with similar learning problems to people with dysphonetic-dyseidetic dyslexia- they have difficulties with phonetics, recognising the shape of words and the synthesis of words.<ref name=Cotton><pubmed>11463183</pubmed></ref> They may also find it difficult when asked to repeat long or large pieces of information.<ref><pubmed>18764980</pubmed></ref>

== Diagnosis ==
[[File:Electrocardiograph_findings_in_dogs_affected_with_DMD.JPG|250px|thumb|Electrocardiograph Findings in DMD dogs]]
* '''Clinical Diagnosis''' - male, progressive symmetrical muscle weakness, symptoms present before age 5, elevated [[#Glossary of terms| '''creatine kinase''']] (CK) blood levels and high levels of liver enzymes (AST and ALT).<ref>http://www.parentprojectmd.org/site/DocServer/Family_Guide.pdf?docID=9321</ref>

* '''Muscle biopsy''' - a sample of muscle can be taken to look for abnormal levels of dystrophin in the muscle. A special stain is used to detect the dystrophin protein. In a unaffected patient, dystrophin will appear as though there is [[#Glossary of terms| '''caulking''']] around the individual muscles cells and it is holding them together like window panes. A patient suffering from DMD will have an absence of the dystrophin.
[[File:Speckle_Tracking_Echocardiograph_of_a_dog_affected_with_DMD.JPG|250px|thumb|Speckle Tracking Echocardiograph]]
* '''Genetic Testing''' - this is achieved through a blood sample analysis. Changes in the DMD gene can be detected through various methods. E.g. Large changes in gene (deletion/duplication) or smaller components that spell out the instructions found within the DMD gene (sequencing). However, results may not be conclusive since changes in the genetic code might go undetected by the methods used.<ref name="genome">http://www.genome.gov/19518854#4</ref>

* '''Physical Examination''' - Myocardial function is an important indicator of DMD. In recent years, it has increasingly become an important cause of death.<ref name=”yugeta”>Naoko Yugeta, Nobuyuki Urasawa, Yoko Fujii, Madoka Yoshimura, Katsutoshi Yuasa, Michiko R Wada et al. Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ): electrocardiographic, echocardiographic, and morphologic studies.BMC Cardiovascular Disorders 2006, 6:47</ref> Therefore, physical examination of cardiac rhythmn and function is essential in the process of diagnosing a patient with DMD. Dystrophin-deficient cardiac muscle is replaced by [[#Glossary of terms| '''fibrotic''']] tissue which can lead to wall motion abnormality, particularly in the left ventricle. These abnormalities can be detected by the following methods:<ref name="Spurney"/>
**Electrocardiography (ECG) - is able to detect myocardial scarring commonly found in DMD patients. The scarring produces [[#Glossary of terms| '''sinus tachycardia''']]. On a electrocardiograph this will appear as tall R-waves and deep Q-waves.<ref name="yugeta"/> Other indicators include an increased heart rate, shortened PQ (PR) interval and arrythmias.
**Holter Monitors - monitors cardiac rhythm for a longer period of time compared to ECG and therefore can provide greater detail of sporadic abnormalities.
**Echocardiography - this method is the most universal standardised assessment of cardiac function. It uses sound waves to produce a 2D image of the heart which is clearer than an X-ray image. Echocardiography can detect myocardial thickening, wall motion abnormalities, enlargement of the left ventricle, and left ventricular [[#Glossary of terms| '''systolic''']] and [[#Glossary of terms| '''dialostic''']] function.<ref name="yugeta"/>
**Cardiac magnetic resonance (CMR) - imaging is being more frequently utilized in DMD patients, providing a sensitive and reliable non-invasive measure of cardiac function.

A combination of these components along with family history confirms the diagnosis.

==Current Treatments==

DMD is a severe neuromuscular disease affecting male children. The progressive muscle deterioration causes the patient to become wheelchair-dependent.<ref>http://www.ncbi.nlm.nih.gov/pubmed/19774532</ref>Although there is no known cure for DMD to date, there are a variety of treatments available which are aimed at managing the symptoms, protecting muscle mass and maximising the quality of life for those who suffer from DMD. Treatments include:

{|border="1"
|-style="background:cadetblue" align="center"
|'''Type of Treatment'''
|'''Description'''
|'''Examples'''
|'''Side Effects'''
|-style="background:"align="center"
|Physical Therapy
|Targets muscle strength and function. Research has shown that long term inactivity can weaken muscles and worsen the condition.
|Regular exercise and physiotherapy sessions. Surgery may also be required in situations of severe [[#Glossary of terms|'''contractures''']] and [[#Glossary of terms|'''scoliosis''']].
|There are no side effects.
|-style="background:"align="center"
|Orthopedic appliances
|These are aimed at improving mobility and the quality of life.<ref>http://jcn.sagepub.com/content/25/9/1116</ref>
|Braces and wheelchairs.
|There are no side effects.
|-style="background:"align="center"
|Medication
|A variety of steroidal drugs are administered to treat symptoms.
|
*Prednisone- is a steroidal immunosuppressant drug targeted at improving strength and function of skeletal muscle.<ref name="genome"/>

*Cyclosporine - has been used in children to treat clinical signs by targeting cardiac [[#Glossary of terms|'''myocytes''']] and consequently decreasing cardiac [[#Glossary of terms|'''hypertrophy''']].<ref> http://www.webmd.com/drugs/mono-9108-CYCLOSPORINE+CAPSULE+-+ORAL.aspx?drugid=5645&drugname=Cyclosporine+OralIt </ref>It weakens the immune system and makes patients susceptible to cancers and other types of infections.
|
Weight gain, high blood pressure, behavioral changes, weakened bones and delayed growth.<ref name="genome"/>

Depression, peptic ulcers, muscle or joint pain, high blood presure, changes in vision, seizures and unusual bleeding or bruising. <ref>http://www.nlm.nih.gov/medlineplus/druginfo/meds/a601207.html#side-effects</ref>

|}

== Future Therapies ==

The following table outlines future therapies, currently being researched, that are targeted at treating and managing DMD.

{|border="1"
|-style="background:cadetblue" align="center"
|'''Future Therapies'''
|'''Description'''
|-style="background:"
|Poloxamer 188 (P188)
|P188 is a non-ionic triblock copolymer, poly(ethylene oxide)80- poly(propylene oxide)27-poly(ethylene oxide)80.
Previous studies have demonstrated the beneficial capacity of P188 in preventing and reducing cardiac damage in DMD affected animals. Based on these animal studies, P188 could become an important acute therapy in DMD. <ref name="Spurney"/P 188 is known to stabilize red blood cell membranes in [[#Glossary of terms|'''sickle cell disease''']].<ref>Ballas SK, Files B, Luchtman-Jones L, Benjamin L, Swerdlow P, Hilliard L, Coates T, Abboud M, Wojtowicz-Praga S, Grindel JM: Safety of purified poloxamer 188 in sickle cell disease: phase I study of a non-ionic surfactant in the management of acute chest syndrome. Hemoglobin 2004, 28(2):85-102.</ref>P188 directly targets membrane instability which is known to be one of the major pathological defects in dystrophin deficient cells.<ref>http://www.biomedcentral.com/1471-2261/11/20#B11</ref>

|-style="background:"
|Losarton
|Losarton is an ATII-type1 receptor blocker which modulates ATII signaling.
Studies have shown decreased myocardial[[#Glossary of terms|''' fibrosis''']] and preservation of cardiac function in DMD mice treated with losarton over a 6 month period. Based on these findings, it is possible that losartan could decrease both skeletal and cardiac muscle fibrosis and preserve skeletal muscle strength and cardiac function in DMD patients. Clinical studies using losartan are currently in progress. <ref name="Spurney"/>
|-style="background:"
|Idebenone
|Idebenone is a synthetic [[#Glossary of terms|'''analog''']] of coenzyme Q10.
It is an antioxidant medication shown to improve mitochondrial respiratory chain function and cellular energy production. A clinical trial was recently completed studying the effects of idebenone in DMD patients with cardiac dysfunction. <ref name="Spurney"/>
|-style="background:"
|Gene Therapy
|Due to the lack of specific medical therapies for DMD at this time, gene therapy offers the promise of a cure by replacing the mutated dystrophin gene in all muscle tissues.<ref name="Spurney"/> However this type of procedure has experienced many complications in regards to the medium of replacement and the possible side effects.
|-style="background:"
|Stem Cell Transplant
|Much of the initial focus was placed on [[#Glossary of terms|'''myoblast''']] transplantation however multiple studies showed little or no success. Research was then expanded to include stem cells that were myogenic precursors. These were obtained from bone marrow, [[#Glossary of terms|'''satellite cells''']], muscle and blood-derived stem cells. Significant further research is required before stem cell therapy becomes a viable treatment strategy. <ref name="Spurney"/>
|-style="background:"
|Utrophin
|Utrophin is an autosomal protein encoded by a gene on chromosome 6 in humans. The primary structure is very similar to that of dystrophin, being 80% identical. Current research observes the upregulation of utrophin to replace dystrophin in DMD patients. Utrophin expression is predominantly driven by two promoters: A and B. Promoter A is responsible for the skeletal muscle-specific expression of utrophin and Promoter B drives expression in endothelial cells.<ref>http://ep.physoc.org/content/early/2011/09/19/expphysiol.2010.053025.long</ref>
|}

==Important Current Research - Utrophin==

Recent research has suggested that utrophin could be highly effective in the treatment of DMD.Utrophin is the [[#Glossary of terms|'''autosomal''']] [[#Glossary of terms|'''homologue''']] of dystrophin<ref name=Blake><pubmed>8866746</pubmed></ref>. Utrophin shares 80% similarity with dystrophin<ref name=NatUtro><pubmed>16595608</pubmed</ref>, with only small changes in the structure of the protein. The gene UTRN encodes utrophin and is located on band q24 of chromosome 6. This gene is approximately 1/3 of the size of the dystrophin gene. During human fetal development, utrophin is found at the [[#Glossary of terms|'''sarcolemma''']] until week 26, when it is replaced by dystrophin, suggesting that utrophin is a fetal isoform of dystrophin.<ref name=Blake/>Utrophin expression is not affected by the DMD gene mutation, and thus could be very important for treating ''all'' DMD patients, regardless of the type of mutation<ref name=Miura><pubmed>16443393</pubmed></ref>. Below are summaries of two important and recent papers on utrophin experiments.

*''Daily Treatment with SMTC1100, a Novel Small Molecule Utrophin Upregulator, Dramatically Reduces the Dystrophic Symptoms in the mdx Mouse''
A group of researchers from England and Italy -Tinsley and Fairclough et. al, (2011)<ref name=Tinsley><pubmed>21573153</pubmed></ref> developed a utrophin up-regulator and tested its effects in mdx mice. This journal describes the results of their experiment. The researchers developed an utrophin up-regulator called SMT C1100, which with daily dosing, significantly reduced the pathology and problems associated with dystrophin deficiency. In their experiment, mdx mice were grouped and treated as per table below: [[Image:Utrophin effects compared to control.jpg|thumb|right|Reduction in pathological features of DMD from use of utrophin up-regulation in comparison to control group]]

{| align="left" style="width:50%; height:100px" border="1"
|- align="center"
| colspan="4" | Sedentary ''mdx'' mice
| colspan="4" | Exercising ''mdx'' mice
|- style="height:50px"
| rowspan="2" colspan="2" | Control (vehicle)
| rowspan="2" colspan="2" | SMT C1100
| rowspan="2" | Control (vehicle)
| rowspan="2" | SMT C1100
| rowspan="2" | Prednisone
| rowspan="2" | SMT C1100 + Prednisone
|}

Analysis was conducted on muscle mechanics, electrophysiology, proteins, RNA, blood and histology from each group of mice. For each variable above, the researchers described in detail the effect of utrophin on the muscle cells and how it was improved.
The results of the experiments showed that SMT C1100 had a significant impact in the treatment of DMD, especially when combined with Prednisone (PDN -type of glucocorticoid used to treat DMD). The increased levels of utrophin significantly reduced the dystrophy pathology of [[#Glossary|'''fibrosis''']] and inflammation of the muscle cells, and led to increased strength and resistance to fatigue after exercise. Other researchers<ref name=Squire><pubmed>12471059</pubmed</ref> have found similar results in experiments using utrophin therapies on mice.

Based on their results, the researchers argue that use of utrophin is very effective as it addresses the primary cause of dystrophy (i.e. it replaces the role of the missing dystrophin) and therefore can treat all mutations of Duchenne muscle dystrophies. They argue strongly the importance of retesting formulations of the utrophin up-regulator and its use in human DMD trials.

*''Naturally occuring utrophin correlates with disease severity in Duchenne muscular dystrophy''
This paper examines human DMD patients, evaluating the role of utrophin in the severity and progression of the disease. Sixteen DMD patients were investigated using muscle [[#Glossary|'''biopsies''']], muscle protein analysis, and ages at moderate disability and wheel-chair bound stage was recorded. Their results showed that DMD sufferers had up to eleven times higher levels of naturally occuring utrophin than normal adult muscle, and that utrophin expression increases with age.

Importantly, a second positive correlation was found between the quantity of utrophin at the first muscle biopsy and age at reaching wheelchair stage. From this, the authors concluded that utrophin has an ameliorating effect on muscle dystrophy and that this extended the time for which the patient could move independently.
The results of this experiment are very similar to other studies<ref name=Tinsley/> demonstrating the positive effect of utrophin in mice. In light of their results, the authors argue that utrophin is a suitable replacement for dystrophin, and is also a viable treatment for human muscle dystrophy disorders. They argue that further research and trials, particularly in humans, is needed.

==Duchenne Muscular Dystrophy Foundations and Organisations==

*'''Muscular Dystrophy Foundation Australia '''- This foundation has been set up to raise awareness of muscular dystrophy disorders and to fund research and support groups across Australia. It has offices in each state that collaborate together. They describe their values as ''innovative, passionate, determined and embracing.
Link to their website: http://mdaustralia.org.au/

*'''Muscular Dystrophy Campaign''' - This group is based in the United Kingdom and has a strong research and clinical trial programme. Similar to the Australian foundation, it also aims to raise funds and awareness of muscular dystrophy disorders.
Link to their website: http://www.muscular-dystrophy.org/

== Glossary of terms ==

*'''Actin:''' a protein that forms the contractile units of muscle cells

*'''Acute gastric dilation:''' short, severe expansion or distension of the stomach, can cause the stomach to twist

*'''Analog:''' a compound that resembles another in structure

*'''Arrhythmias:''' abnormal heart contractions/irregular heart beat

*'''Atrophy:''' wasting away or disintegration of; decrease in size, owing to disease, misuse, injury

*'''Autosomal:''' a non-sex chromosome

*'''Base pair:''' two complementary bases in a nucleic acid molecule

*'''Cardiomyopathy:''' heart muscle disease

*'''Caulking:''' to make airtight or watertight by sealing or filling

*'''Cerebral cortex:''' unmyelinated neurons (grey matter) that forms the outer layer of the cerebrum

*'''Cytoplasm:''' material within a cell

*'''Cytoskeleton:''' microscopic skeleton of a cell within the cytoplasm, composed of protein

*'''Creatine kinase:''' an enzyme normally highly concentrated within muscle cells. As muscle cells degenerate, their contents are released into the bloodstream. Therefore elevated levels of creatine kinase can be detected by a blood test and is a measure of muscle damage

*'''Dendrites:''' thin extension of a nerve cell, branches out to receive nerve impulses from other neurons

*'''Dominant:''' a trait determined by an allele that is expressed over another present allele

*'''Dystrophin:''' a protein involved in muscular contraction

*'''Dystrophin-associated protein complex (DAPC):''' a multiprotein complex that includes dystrophin and other associated proteins

*'''Dystrophy:''' degenerative disorder; weakens and atrophies

*'''Extracellular matrix:''' network of connective tissues and fibres that provide support and exist outside the cell

*'''Fibrosis:''' a repair process by the body in response to injury- damaged tissue is replaced by connective tissue and often results in a scar

*'''Fibrotic:'''excess of fibrous connective tissue in an organ

*'''Filamentous:''' thread-like cells

*'''Gene:''' sequence of nucleotides forming part of a chromosome

*'''Genome:''' the complete set of genetic material in a cell or organism

*'''Hippocampus:'''sea-horse shaped mass of grey matter found on the floor of the lateral ventricles in the brain -functions in long term memory, emotion and controls the autonomic nervous system and is classified as part of the limbic system

*'''Homologue:''' a chromosome that is similar in physical attributes and genetic information to another chromosome with which it pairs during meiosis

*'''Hypercapnia:''' abnormally high levels of CO2 in the bloodstream

*'''Hypertrophy:'''enlargement of organ or tissue by increasing the size of cells

*'''Joint contractures:''' stiffness of the joints, prevents movement or full extension and flexion

*'''Macrophage:''' lymphatic cell found throughout the body; clears dead cells and debris

*'''Muscle contraction:''' process in which muscles shorter and are made tighter under neuronal control

*'''Muscle fiber:''' elongated contractile cell

*'''Myoblast:''' precursor of skeletal muscle tissue. Fusion of myoblasts gives rise to myotubes which eventually develop into skeletal muscle fibres

*'''Myocyte:''' a muscle cell

*'''Necrosis:''' cell death in a particular region of tissue

*'''Nucleotides:''' compounds that form the basic structural units of nucleic acids

*'''Phenotype:''' the physical expression of the genotype

*'''Plasma membrane:''' composed of lipids and proteins, forms the external boundary of the cytoplasm

*'''Protease:''' an enzyme that breaks down proteins and peptides

*'''Proximal:''' towards the point of attachment

*'''Pseudohypertrophy:''' enlarged muscles due to large amounts of fat and connective tissue; characteristic of DMD. Usually of the calves but may be found in other muscles such as the deltoids and serratus anterior

*'''Pseudo-obstruction:''' when a patient expresses the symptoms of intestinal blockage, but there is no physical blockage. Can be acute or chronic

*'''Pulmonary aspiration:''' entry of foreign material (food, drink, stomach contents like bile or vomit, pharyngeal secretions) from the oesophagus into the trachea or lower respiratory system.

*'''Recessive:''' the opposite of Dominant

*'''Sarcolemma:''' the thin membrane of striated muscle fibers

*'''Satellite Cells:'''

*'''Sacroplasmic:''' (sacroplasma) The cytoplasm of striated muscle cells

*'''Scoliosis:''' abnormal curvature of the spine

*'''Signal transduction:''' internal cell signalling process

*'''Sinus tachycardia:''' rhythm in which the rate of impulses arising from the SA node is elevated

*'''Soma:'''body of the neuron cell

*'''Systolic:''' maximum blood pressure during contraction of the heart

*'''Transmembrane:''' existing across a membrane

*'''X chromosome:''' sex chromosome, two are represent in females and only one is present in male cells

== References ==
<references/>

Kornberg, R. (2007), "Chromatin and Transcription", in Tsonis, P. (ed.), From DNA to Proteins: The Multiple Levels of Regulation, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://www.hstalks.com/bio)