Talk:2011 Group Project 5
--Mark Hill 07:35, 30 September 2011 (EST) Currently all students originally assigned to each group are listed as equal authors/contributors to their project. If you have not contributed the content you had originally agreed to, nor participated in the group work process, then you should contact the course coordinator immediately and either discuss your contribution or request removal from the group author list. Remember that all student online contributions are recorded by date, time and the actual contributed content. A similar email reminder will be sent to all current students.
Please note the Universities Policy regarding Plagiarism
In particular this example:
- "Claiming credit for a proportion of work contributed to a group assessment item that is greater than that actually contributed;"
Academic Misconduct carries penalties. If a student is found guilty of academic misconduct, the penalties include warnings, remedial educative action, being failed in an assignment or excluded from the University for two years.
2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip
It looks like it is going to be late nights all round. We should try and pump out an intro in that time tomorrow as well as at least one image? --Tara Lofthouse 18:52, 14 September 2011 (EST)
Okay, Tomorrow at 10am it is. I'll finish my stuff off tonight (it looks like being a late night :P). I'm assuming that it doesn't have to be perfect by tomorrow. It just needs to look alright, so that people can give us feedback before we finish it, yeah? Also, Boris, Interview is on the 27th. I was just visiting a friend. I'll tell you how it goes though, when it does happen. --Ziggy Harrison-Tikisci 17:43, 14 September 2011 (EST)
I can make it at 10am on Thursday as well --Tara Lofthouse 12:08, 14 September 2011 (EST)
Ooo, interview? How'd it go? I don't have time to meet up today (Wednesday), but I can see you guys in the lab at 10 tomorrow, before the class. --Boris Zolotarev 10:39, 14 September 2011 (EST)--Boris Zolotarev 10:39, 14 September 2011 (EST)
Hey Guys, Sorry I've been in Melbourne for the week, so haven't done any work. Getting on it now. Going to do all my referencing, editing etc. Wanted to ask if there is a time when we can get together, go through it all and make it pretty. Did we just want to do this before our lab on thursday, or if you guys have some time on wednesday afternoon? Furthermore, how harsh is the criticism/feedback? Doesn't mince his words, does he? --Ziggy Harrison-Tikisci 12:51, 12 September 2011 (EST)
Hey Boris yes i am experiencing the same problem. I cannot see the references and the reference list looks like a bunch of arrows facing superiorly. I got a bit worried but then checked the other groups and they had the same issue. I'm not sure what we can do? Let me know. ---Sandra Issa 09:49, 9 September 2011 (EST)
WHAT HAPPENED TO OUR REFERENCES. Can you guys do me a favour and tell me if you can see them? I was trying to put in an image just then and when I did the save it came up with references wiped. I tried undoing my last edit to no avail. There are still 30 something references, there's just nothing IN them. When I finished my word edit earlier today I actually saved the ENTIRE script as a word document; when I tried to rewrite EVERYTHING with that same (working) script it still came up with stuffed up references.
Let me know if you guys see the same problem. If you do, I'll have to get in contact with Mark Hill to fix the script. --Boris Zolotarev 23:31, 8 September 2011 (EST)
I hate how the times shown on the editing thing are totally out of whack....can I post anything up at the moment? >< --Boris Zolotarev 23:27, 7 September 2011 (EST)
Hey guys, i have just added the diagnosis part of our page and have also finished the treatment. Let me know if you think the treatment is too long? Or if you want to make any changes to the "Recent Research" part of our page.
Also, i will add in more references for this part very soon. I have put in a general reference (review article) but will make sure i include all references used very soon.
Have a good night, --Sandra Issa 21:16, 7 September 2011 (EST)
Suggestion: rename Development of disease to Progression of disease. Also, I should have a heap up later tonight, I'm compiling it all in a separate document at the moment.
--Boris Zolotarev 15:39, 7 September 2011 (EST)
Hey guys, just letting you know that i have found a great article which addresses many current 'treatments' for FXS. Also, i have found another article which summarises the current methods of diagnosing FXS. I will add this information (what i think is most relevant from the articles) onto our group page under the headings "treatment" and "diagnosis" very soon. Please feel free to add in anything that you believe i have not addressed under these headings. Also, i will try to edit our page as a whole soon so that it looks more uniform in appearance. Over the next couple of days we should all read each of the sections and try to add in additional information that someone else may have missed. Also, a reminder to keep an eye out for relevant pictures that have unrestricted access to add onto our page! Cheers, --Sandra Issa 12:32, 5 September 2011 (EST)
Hey, I'm doing a whole bunch now. I'll properly reference it all later, but I'm getting a lot of it off the american National Institute of Health. They've got references for all of it. So when I have more time, I'll go through those references, add them, and edit the information. So, what I put on the group page will just be an overview. Also, you people should go to bed earlier :) http://www.nichd.nih.gov/publications/pubs/fragileX/sub6.cfm --z3290618 09:49, 1 September 2011 (EST)
z3290808: I don't know why it wouldn't let you save, i wasn't editing at that time. Try again and if it doesn't work maybe paste your work here with your references and one of us can put it onto the project page for you?
Boris: At least something is up :) My section needs a lot more editing and a lot more cross checking with other references as well.. Any progress is good progress at the moment --Tara Lofthouse 03:35, 1 September 2011 (EST)
Heya, I took a stab at my section but I'm a bit dead at the moment (points to timestamp). I'll try get some more done tomorrow between the lecture and lab.
On the plus side, I added another 6 or 7 references to our thingy ^^
--Boris Zolotarev 01:28, 1 September 2011 (EST)
Guys it's not letting me save what i have written onto the group page! Is anyone currently on and trying to edit at this same time? --z3290808 22:41, 31 August 2011 (EST)
Yo Boris, You do Etiology, I'll do signs and symptoms. We can work towards the middle. That leaves history and epidemiology to Tara and Recent research to Sandra. And then we can all refine it/make an intro. We can at least do that to start with. Also: can everyone contribute to the glossary. If you find any terms that people (eg. me) wont understand, please keep them.--Ziggy Harrison-Tikisci 10:10, 25 August 2011 (EST)
The only reason why we need to put our names down now is to satisfy the weekly individual assessment but of course we can change things. Just put your name down for epidemiology or whatever was left over and we'll discuss it tomorrow. Maybe if we could get to the lab 10-15min earlier because we never get enough time at the end of the lab?
--Tara Lofthouse 19:50, 24 August 2011 (EST)
Just skimmed through this (damn I left it late >< ), should I nominate something now or should we discuss it tomorrow? Also, what do you guys think of having some sort of realtime chat method? Facebook or something of the sort... --Boris Zolotarev 19:17, 24 August 2011 (EST)
Yeah i know but the ones i put my name down for are really not that lengthy. We definitely need to have a chat tomorrow. --Tara Lofthouse 17:45, 24 August 2011 (EST)
Hey guys, you haven't left much for Boris and i to do lol .. I don't mind doing the recent research part - focussing on autism and fragile x.. but then i don't know what Boris would do? I will sign my name for now but i think we will have to change it around a little to better make the work load equally spread.
Cheers, --Sandra Issa 16:17, 24 August 2011 (EST)
I've taken it all on board and changed it. I'm fine for you to do whatever you want but doing both the genetic component and the signs and symptoms might be a lot of work. As long as everything is spread evenly i don't mind :)
--Tara Lofthouse 16:35, 23 August 2011 (EST)
Hey, I was wondering if anyone minds if I do 'Genetic contribution'. Also, is it okay if I follow the timeline of the disease? I will start with the chromosome, saying what the defect causes at a molecular level, and then when it first presents, and how it affects the development etc up until how it presents in the adult. Which means I'd probably do "Signs and symptoms (clinical Presentation)" as well. ALSO, we need to do a brief history of the disorder. So, below I've just tweaked the layout Tara and Sandra put up: let me know what you think
- History of Disease
- Genetic contribution
- Development of Disease
- Fetal Development
- At birth
- In Adult
- Signs and symptoms
- Recent research
- Fragile X and Autism
--z3290618 15:18, 23 August 2011 (EST)
Yeah, i think it makes sense how you've got it Sandra. However like Boris said maybe instead of having the heading "Autism and Fragile X Syndrome" maybe we could have recent research/current studies or something along those lines and include it there along with diagnosis and treatment? Do you think that etiology is too similar to genetic contribution?
ALSO!!! What headings would you like to research? I set up a "Who's doing what?" heading on this page to sign your name next to.
--Tara Lofthouse 12:39, 23 August 2011 (EST)
Hey guys, i have come up with a couple of headings that we can use:
- Introduction (short summary)
- Signs and Symptoms (Clinical Presentation)
- Genetic Contribution
- Autism and Fragile X syndrome
Tara i also like the format that you have included below.. i basically have made something similar but in different order based on what i think should come first perhaps? The ones with a question mark beside them are ones that i am unsure if we should include or not. Let me know what you think! Cheers, --Sandra Issa 12:03, 23 August 2011 (EST)
Hahaha of course it's your place to say so.. good suggestion, i'll fix it up now and if we want to change it again than that's no problem. I just thought i'd put something up to get started and we can go from there. What i've done is no where near completed. --Tara Lofthouse 18:52, 22 August 2011 (EST)
(I know it's not my place to say so before I've submitted my own suggestion but) I think I'd put "Autism and Fragile X Syndrome" within the "recent research" subtopic. I'll put up a suggestion by tomorrow evening, if not earlier. --Boris Zolotarev 09:27, 22 August 2011 (EST)
Hello everyone, what do you think about using the following headings for our project? Are there ones that you think we could omit or ones that you would like to add? We also need to decide on who is doing what.
- Signs and symptoms
- Recent research
- Autism and Fragile X Syndrome
--Tara Lofthouse 16:26, 21 August 2011 (EST)
Here's another interesting topic.
Congenital Hypomyelinating Neuropathy
What do you guys think you of this topic Congenital Hypomyelinating Neuropathy?
There are quite a few articles on it:
Clinical Phenotypes of Different MPZ (P0) Mutations May Include Charcot–Marie–Tooth Type 1B, Dejerine–Sottas, and Congenital Hypomyelination.
Analysis of congenital hypomyelinating Egr2 Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination.
P0 Glycoprotein Overexpression Causes Congenital Hypomyelination of Peripheral Nerves.
Congenital hypomyelinating neuropathy, central dysmyelination, and Waardenburg–Hirschsprung disease: Phenotypes linked by SOX10 mutation.
A lot of them overlap with their findings and the focus of their studies, so it seems to be a pretty thorough topic.
--Boris Zolotarev 21:03, 7 August 2011 (EST)
I’m all for doing Congenital Hypomyelinating Neuropathy as our topic.
Here are some articles I have found:
- Describes the engineering and characterisation of a mouse carrying the I268N mutation in Egr2.
- The proper formation of myelin by Schwann cells requires a series of transcription factors including SOX10, SCIP/Oct6, Egr2, and Nab1/Nab2.
- A loss of these transcription factors disrupts the myelination process, as does persistent overexpression.
- This was observed in patients with recessively inherited Charcot–Marie–Tooth (CMT) disease type 4E, which is predicted to alter the ability of Egr2 to interact with the Nab transcriptional coregulatory proteins.
- Charcot–Marie–Tooth disease (CMT) is a common inherited disorder of peripheral nerves characterized by progressive sensory loss and weakness beginning in the feet and legs, and later progressing to the hands
- Mice homozygous for Egr2I268N developed a congenital hypomyelinating neuropathy similar to human counterparts.
- Egr2I268N is expressed at normal levels in developing nerve but is unable to interact with Nab proteins or to properly activate transcription of target genes critical for proper peripheral myelin development.
- Egr2I268N/I268N mutant mice maintain normal weight and have only mild tremor until 2 weeks after birth, at which point they rapidly develop worsening weakness and uniformly die within several days. Nerve electrophysiology revealed conduction block, and neuromuscular junctions showed marked
- Describes the symptoms of two patients with congenital hypomyelinating neuropathy
- Hypotonia = low muscle tone (amount of tension or resistance to movement in a muscle)
- Areflexia = absence of neurologic reflexes such as the knee jerk
- Distal muscle weakness
- Atrophy = wasting of a part of the body
- Exceedingly slow nerve conduction velocities
- Usually leading to early death or severe disability.
- It contains great images of the histology of the condition as well as the actual patients
- It contains a detailed recount of sural nerve biopsies of the patients
- It compares the symptoms of congenital hypomyelinating neuropathy in Trembler mice as they are very similar to human symptoms
- Review of previously reported cases of congenital hypomyelinating neuropathy (CHN) aswell as two unrelated females with CHN
- The first patient is now 9 years old and has showed continual improvement of motor function even though her follow up nerve conduction velocities remained unchanged
- The second patient is now 5 years old and has also showed continual motor function improvement since her first visit even though her follow up nerve conduction velocities also remained unchanged
--Tara Lofthouse 12:22, 9 August 2011 (EST)
Fragile X Syndrome
Hey guys, I had a look at Congenital Hypomyelinating Neuropathy and to be honest i did not find it very appealing. I found the disorder "Fragile X Syndrome" to be very interesting! Can you guys please check out the following link on Fragile X Syndrome and let me know if the disease also interests you!? I found the information on it is quite extensive and the disease is well known. If you do not want to base our project on this syndrome, i am sure we can decide on one we can all enjoy studying! :)
Here are some interesting articles that i have found on Fragile X Syndrome:
- Review Article: Fragile X syndrome: from gene discovery to therapy 
- This review focuses on the molecular and biochemical pathways shown to be relevant in the Fragile X Syndrome. It describes that a mutation in the FMR-1 gene was found to lead to Fragile X Syndrome due to excessive repeats of the trinucleotide sequence CGG which is known to inactivate the FMR-1 gene, making the X chromosome fragile and prone to breakage. This review article also demonstrates the many vital functions of the FMR-1 gene such as its role in RNA transport and stability, thus absence of the protein transcribed and translated from this gene is thought to affect brain development and thus leads to signs of mental retardation.
- Research Article: DNA methylation represses FMR-1 transcription in fragile X syndrome 
- This research article explores the two molecular differences of the FMR-1 gene in normal individuals vs. those with Fragile X Syndrome. These differences are an increase in size of an FMR-1 exon containing a CGG repeat and abnormal methylation of a CpG island 250 bp proximal to this repeat. This research article also shows how these two abnormalities repress transcription of the FMR-1 gene, leading to the absence of the FMR-1 protein which is thought to be the contributing factor to the Fragile X phenotype.
--Sandra Issa 19:53, 9 August 2011 (EST)
Here are some articles I have found for Fragile X syndrome:
Research Article: The state of synapses in Fragile X Syndrome 
- Fragile X Syndrome is the most common inherited form of mental retardation and a leading genetic cause of autism.
- Evidence that suggests alterations in synapse number, structure and function are associated and contribute to both Fragile X Sydrome and autism.
- Fraile X Syndrome is caused by loss of function of the Fmr1 gene which encodes the RNA binding protein, FMRP (FMRP is present at synapses where it associates with mRNA and polyribosomes).
- FMRP is also has a role in synapse development, elimination and plasticity.
- An understanding of the molecular and synaptic function of FMRP, as well as the consequences of its loss, has led to the early developments of therapeutic strategies for Fragile X Syndrome.
Research Article: Fragile x syndrome: history, diagnosis, and treatment. 
Review Article: Systematic review of pharmacological treatments in fragile X syndrome 
Review Article: FMR1 and the fragile X syndrome: human genome epidemiology review 
--Tara Lofthouse 14:37, 16 August 2011 (EST)
File:FMR4 is silenced in fragile X syndrome
--Sandra Issa 10:20, 14 August 2011 (EST)
--Tara Lofthouse 13:49, 17 August 2011 (EST)
Like? File: Fragile site appearance and distribution --Ziggy Harrison-Tikisci 08:55, 18 August 2011 (EST)
File: FXR1 and FXR2 crystal structures
--Boris Zolotarev 11:00, 18 August 2011 (EST)
Who's doing what?
- Introduction = DO AT THE END!!!!
- History of Disease = Tara
- Epidemiology = Tara
- Etiology = Boris
- Signs and symptoms = Ziggy
- Physical phenotype
- Social interaction
- Intellectual development
- Recent research = Sandra
- Fragile X and Autism
Just leaving this here for the next hour, so that I don't have to retype it all (can't get wifi in the embryo lab).
The hallmark of the fragile X syndrome is mental retardation, which was noted as early as 1943 in a report of a large family with 11 mentally retarded males and two mildly retarded females. 64 The clinical phenotype associated with the syndrome has since been widened to include a variety of cognitive, physical, and behavioral characteristics (reviewed in Mazzocco). 65 Almost all males with the full mutation exhibit some clinical features of the fragile X syndrome. Also, most affected males do not reproduce, presumably due to the severity of mental retardation. With regard to cognitive function, affected males often exhibit developmental delay very early in childhood. By the age of 3 years, most males will test in the mentally retarded range. 66 Ultimately, almost all males with the fragile X syndrome are mentally retarded, with severity ranging from profound (IQ <20) to mild mental retardation (IQ 50–70), with most being moderately retarded (IQ 40–54) (reviewed in Hagerman). 67 Physically, adult males often have a long narrow face, prominent ears, a prominent jaw, and macroorchidism (reviewed in Hagerman). 67 Other common physical features include a high arched palate, hyperextensible finger joints, double jointed thumbs, single palmar crease, hand calluses, velvet-like skin, flat feet, and mitral valve prolapse (reviewed in Warren and Sherman). 8 Males with the fragile X syndrome also tend to exhibit behavioral features such as hyperactivity, social anxiety, perseverative speech and language, tactile defensiveness, stereotypies (e.g., hand-flapping), and hand biting (reviewed in Hagerman). 67 Autistic-like behavior is also described in these males, with as many as 25% of males with the fragile X syndrome meeting the diagnostic criteria for autism. 68 The association of fragile X with autism, however, is not clear because the proportion of males with the fragile X syndrome meeting the diagnostic criteria for autism seems to diminish with age. 68
Physical phenotype Before puberty, children with Fragile-X tend to have no discernable differences in physical appearance. They may have a broad forehead or a slightly larger size head. At puberty, these children begin to develop the physical signs recognized with Fragile-X, such as longer faces, larger jaws and ears. Furthermore, they tend to have impaired growth, and will not achieve a height that one might expect (based on familial relations, or population averages). Males may also develop macro-orchidism: enlargement of the testicles. Fragile-X patients may also have loose connective-tissues, allowing their joints to be more flexible that normal. This may cause complications arising from increased risk of hernia as well as problems associated with other connective tissues such as: heart-valve weaknesses resulting in murmur. Later in life, these men may develop a tremor and experience difficulty walking.
Social interaction Children with Fragile-X tend to experience social anxiety, feeling awkward and uncomfortable in new environments and situations. Often, they may avoid social interactions, due to the anxiety, and tend not to seek contact with others. Their anxiety often manifests itself as discontinuous speech and a lack of eye contact.
Results indicate that compared to the control group, individuals with FXS exhibited decreased activation of prefrontal regions associated with complex social cognition, including the medial and superior frontal cortex, during successful face encoding. Further, the FXS and control groups showed significantly different relationships between measures of social anxiety (including gaze-fixation) and brain activity during face encoding. These data indicate that social anxiety in FXS may be related to the inability to successfully recruit higher level social cognition regions during the initial phases of memory formation. Reference: Prefrontal social cognition network dysfunction underlying face encoding and social anxiety in fragile X syndrome.
Intellectual development As a generalisation, the majority of Fragile-X patients have an IQ between 1 and 2 standard deviations below the population mean. This equates to around 40-85. Few Patients lie out-side this range, with approximately 20% within the ‘normal’ range (85-115) and less below 40. Females however, show lower impairment, with only one-third having IQs within the ‘mental retardation’ range. Generally, Fragile-X patients have trouble with forming abstract ideas, planning and problem solving. Conversely, they tend to have a good memory for pictures and visual patterns, and may be better adept at following instructions if presented in picture format. Compared to their unaffected siblings, children with FXS obtained significantly lower percentage correct scores on all subtests of the WISC at both time points. During the time between the first and second assessments, the annual rate of intellectual development was approximately 2.2 times faster in the unaffected children compared to the children with FXS. Levels of the fragile X mental retardation protein (FMRP) were highly associated with intellectual ability scores of the children with FXS at both time points.
Studies of intellectual function in FXS often demonstrate a mean IQ decline of 4 to 9 standardized points over intervals ranging from several months to 13 years. Reference: Longitudinal Changes in Intellectual Development in Children with Fragile X Syndrome
Working Memory First, when individuals affected by the premutation are examined as a group, they exhibit a weakness only for tasks that reflect functioning of the central executive subcomponent of working memory.
Second, when both permutation sub-groups are examined together, the extent of the central executive deficit is significantly correlated with larger CGG repeat expansions.
For permutation males who are asymptomatic, mild executive dysregulation, inhibitory deficits that worsen with age, and declarative verbal learning and memory are notable.
The detection of a deficit in the central executive component of working memory in the fourth decade of life that progressively deteriorates with age suggests a cumulative process that may be a cognitive correlate to the underlying degenerative process identified in premutation males.
The significant correlation between CGG repeat length and central executive working memory in asymptomatic carrier males suggests greater neuropathology in carrier males with larger expansions in FMR1 mRNA transcripts. Reference: Lifespan changes in working memory in fragile X premutation males
Emotional characteristics Fragile-X children often are easily upset or overwhelmed. New situations can easily frighten them. Upon entering an unfamiliar situation, some tend to cry, whilst others may become tense. These may often lead to tantrums or repetitive tics. During puberty and teen years, hormone levels may exaggerate this, making the tantrums more violent and the patients largely more aggressive. Furthermore, the usual anxiety experienced with difficult tasks may take longer to abate, meaning the patient may take longer to calm-down.
Language and Speech Often these children have problems with coherence, word pronunciation and correct grammar use. This impairs their ability to properly communicate meaning. More serious speech problems are associated with vocal processing, such as: moderating tone, pitch or loudness as well as coordinating the movements needed to vocalize sounds. Furthermore, they may have difficulties processing spoken information and, as shown above, will be better at following instructions if presented in picture format. These children may stutter, omit sounds out of their words, repeat themselves, or restart the same sentence many times. They may also speak fast and/or mumble. It is important to note, that some of their disability to communicate can be attributed to the shyness and social anxiety, while specific deficits may be due to sensory overload, rather than specific neural problems with control of speech and language.