2011 Group Project 5 - Revision history

Z8600021 at 07:29, 7 Mayıs 2018

2018-05-07T07:29:08Z

Z8600021 at 23:07, 13 March 2018

2018-03-13T23:07:22Z

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	{{2011Projects}}		{{2011Projects}}
	[[Category:Fragile X Syndrome]]		[[Category:Fragile X Syndrome]][[Category:X Chromosome]]

Z8600021 at 23:11, 20 February 2014

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	{{2011Projects}}		{{2011Projects}}
			[[Category:Fragile X Syndrome]]

S8600021 at 00:55, 19 October 2011

2011-10-19T00:55:51Z

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	{{2011ProjectsMH}}		{{2011ProjectsMH}}



	~~{{2011Projects}}~~

	= Fragile X Syndrome =		= Fragile X Syndrome =

S8600021: Protected "2011 Group Project 5": Protect from student change ([edit=sysop] (indefinite) [move=sysop] (indefinite))

2011-10-13T06:25:28Z

Protected "2011 Group Project 5": Protect from student change ([edit=sysop] (indefinite) [move=sysop] (indefinite))

← Older revision	Revision as of 16:25, 13 October 2011
(No difference)

Z3290815: /* Glossary */

2011-10-13T04:48:05Z

Glossary

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	'''Phenotypic abnormality:''' a deviation from the normal or differing from the typical, in regards to the observable characteristics or traits of the organism.		'''Phenotypic abnormality:''' a deviation from the normal or differing from the typical, in regards to the observable characteristics or traits of the organism.

			'''Prolapse:''' literally means “to fall out” and is a condition where organs, such as the uterus, fall down or slip out of place.

	'''Psychopedagogic:''' combination of two main branches of study; pedagogy and psychology. Pedagogy is the study of the process of teaching and psychology is the science of behaviour and mental processes.		'''Psychopedagogic:''' combination of two main branches of study; pedagogy and psychology. Pedagogy is the study of the process of teaching and psychology is the science of behaviour and mental processes.

Z3290815: /* Physical phenotype */

2011-10-13T04:45:12Z

Physical phenotype

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	At puberty, these children begin to develop the physical signs recognized with Fragile-X, such as longer faces, larger jaws and ears<ref name="PMID2018070"><pubmed>2018070</pubmed></ref>. Furthermore, they tend to have impaired growth, and will not achieve a height that one might expect (based on familial relations, or population averages).		At puberty, these children begin to develop the physical signs recognized with Fragile-X, such as longer faces, larger jaws and ears<ref name="PMID2018070"><pubmed>2018070</pubmed></ref>. 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 [[#Glossary \| '''macroorchidism''']]: enlargement of the testicles.		Males may also develop [[#Glossary \| '''macroorchidism''']]: enlargement of the testicles.
	Fragile-X patients may also have loose connective-tissues<ref name="PMID2195034"><pubmed>2195034</pubmed></ref>, allowing their joints to be more flexible ~~that~~ normal. This may cause complications arising from increased risk of [[#Glossary \| '''hernia''']] as well as problems associated with other connective tissues such as: heart-valve weaknesses resulting in murmur.		Fragile-X patients may also have loose connective-tissues<ref name="PMID2195034"><pubmed>2195034</pubmed></ref>, allowing their joints to be more flexible than normal. This may cause complications arising from increased risk of [[#Glossary \| '''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.		Later in life, these men may develop a tremor and experience difficulty walking.

	Physically, adult males often have a long narrow face, prominent ears, a prominent jaw, and macroorchidism. 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<ref name="PMID2018070"/><ref name="PMID2195034"/>. Mitral valve prolapse has been shown to in late adolescence<ref name="PMID8464655"><pubmed>8464655</pubmed></ref>. Males with the fragile X syndrome also tend to exhibit behavioral features such as hyperactivity, social anxiety, perseverative speech and language, tactile defensiveness, stereotypes (e.g., hand-flapping), and hand biting.		Physically, adult males often have a long narrow face, prominent ears, a prominent jaw, and macroorchidism. 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<ref name="PMID2018070"/><ref name="PMID2195034"/>. Mitral valve [[#Glossary \| '''prolapse''']] has been shown to in late adolescence<ref name="PMID8464655"><pubmed>8464655</pubmed></ref>. Males with the fragile X syndrome also tend to exhibit behavioral features such as hyperactivity, social anxiety, perseverative speech and language, tactile defensiveness, stereotypes (e.g., hand-flapping), and hand biting.

	=== Social interaction ===		=== Social interaction ===

Z3290815: /* History of the disease */

2011-10-13T04:35:44Z

History of the disease

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	\|-		\|-
	\| valign="top" bgcolor="mistyrose"\|'''1943'''		\| valign="top" bgcolor="mistyrose"\|'''1943'''
	\| valign="top" bgcolor="lavenderblush"\|Martin and Bell first reported that the excess number of retarded males in the population was due to a sex linked inheritance. The two also noted that there was a lack of unusual physical features related to the mental retardation, including the shape of the head and face. Therefore Martin and Bell were also the first to report sex linked mental retardation without [[#Glossary \| '''microcephaly''']] or [[#Glossary \| '''microphthalmia''']]<ref name="PMID6348096 "/>.		\| valign="top" bgcolor="lavenderblush"\|Martin and Bell first reported that the excess number of retarded males in the population was due to a sex linked inheritance. The two also noted that there was a lack of unusual physical features related to the mental retardation, including the shape of the head and face. Therefore Martin and Bell were also the first to report sex linked mental retardation without [[#Glossary \| '''microcephaly''']] or [[#Glossary \| '''microphthalmia''']]<ref name="PMID6348096 "/>. For this reason, Fragile X syndrome is also referred to as Martin-Bell syndrome.
	\|-		\|-
	\| valign="top" bgcolor="mistyrose"\|'''1969'''		\| valign="top" bgcolor="mistyrose"\|'''1969'''

Z3290815: /* Epidemiology */

2011-10-13T04:29:33Z

Epidemiology

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	* African Americans had a frequency of 1 in 124<ref name="PMID21116185"/>		* African Americans had a frequency of 1 in 124<ref name="PMID21116185"/>
	* Ashkenazi Jewish had a frequency of 1 in 134<ref name="PMID21116185"/>.		* Ashkenazi Jewish had a frequency of 1 in 134<ref name="PMID21116185"/>.


	[[File:Fragile x inheritance.jpg\|centre\|400px\|Fragile X inheritance for Non-symptomatic parents]]		[[File:Fragile x inheritance.jpg\|centre\|400px\|Fragile X inheritance for Non-symptomatic parents]]

Z3290815: /* Related Links */

2011-10-13T04:21:37Z

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	* [http://embryology.med.unsw.edu.au/Defect/fragilex.htm Abnormal Development - Fragile X]\| This page describes Fragile X Syndrome as an example of abnormal development. It includes an introduction, some recent findings, symptoms, the FMR protein responsible for Fragile X, diagnostic testing and www links.		* [http://embryology.med.unsw.edu.au/Defect/fragilex.htm Abnormal Development - Fragile X] - This page describes Fragile X Syndrome as an example of abnormal development. It includes an introduction, some recent findings, symptoms, the FMR protein responsible for Fragile X, diagnostic testing and www links.

	* [[Abnormal Development - Genetic\|Abnormal Genetic Development]]\| This page provides a good understanding of how genetic abnormal development occurs; especially in regards to it’s relationship with age, ethnicity, inheritance and prenatal testing.		* [[Abnormal Development - Genetic\|Abnormal Genetic Development]] - This page provides a good understanding of how genetic abnormal development occurs; especially in regards to it’s relationship with age, ethnicity, inheritance and prenatal testing.

	* [[Neural System - Abnormalities\|Abnormal Neural Development]] - This page is related to our group page. It describes examples of abnormalities associated with the nervous system which are congenital and environmentally derived. Two such examples which are of interest to us are Fragile X Syndrome and Autism.		* [[Neural System - Abnormalities\|Abnormal Neural Development]] - This page is related to our group page. It describes examples of abnormalities associated with the nervous system which are congenital and environmentally derived. Two such examples which are of interest to us are Fragile X Syndrome and Autism.

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	Fragile-X syndrome (FXS) is a [[#Glossary \| '''congenital disorder''']] resulting from an abnormality on the X-chromosome. FXS is named for the fragile site on the X chromosome found in those affected with this syndrome. The fragile site is known as FRAXA ('''Fra'''gile site on the '''X''' chromosome site '''A''') which appears as a gap, constriction or break in [[#Glossary \| '''metaphase''']] chromosomes as shown in figure 1~~<ref name="~~PMID19465392~~"><pubmed>19465392</pubmed></ref>~~. Specifically it is caused by [[#Glossary \| '''methylation''']] of the CGG triplet resulting in its amplification. The expansion of the [[#Glossary \| '''nucleotide triplet''']] (CGG) causes the extremity of the long arm of chromosome X to appear elongated,~~<ref name="~~PMID19718005~~"><pubmed>19718005</pubmed></ref>~~ creating a site of constriction which becomes fragile and is prone to breaking~~<ref name="~~PMID6348096~~"><pubmed>6348096</pubmed></ref>~~. The amplification of this codon also results in the [[#Glossary \| '''silencing''']] of the FMR1 gene.		{{Fragile X syndrome}} (FXS) is a [[#Glossary \| '''congenital disorder''']] resulting from an abnormality on the X-chromosome. FXS is named for the fragile site on the X chromosome found in those affected with this syndrome. The fragile site is known as FRAXA ('''Fra'''gile site on the '''X''' chromosome site '''A''') which appears as a gap, constriction or break in [[#Glossary \| '''metaphase''']] chromosomes as shown in figure 1{{#pmid:19465392\|PMID19465392}}. Specifically it is caused by [[#Glossary \| '''methylation''']] of the CGG triplet resulting in its amplification. The expansion of the [[#Glossary \| '''nucleotide triplet''']] (CGG) causes the extremity of the long arm of chromosome X to appear elongated,{{#pmid:19718005\|PMID19718005}} creating a site of constriction which becomes fragile and is prone to breaking{{#pmid:6348096\|PMID6348096}}. The amplification of this codon also results in the [[#Glossary \| '''silencing''']] of the FMR1 gene.


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	\| valign="top" bgcolor="mistyrose"\|'''2001'''		\| valign="top" bgcolor="mistyrose"\|'''2001'''
	\| valign="top" bgcolor="lavenderblush"\|Hagerman and colleagues first recognized Fragile X-associated tremor/[[#Glossary \| '''ataxia''']] syndrome (FXTAS)~~<ref name="~~PMID11445641~~"><pubmed>11445641</pubmed></ref>.~~ FXTAS is a disorder that is under-recognized because the first published report was only in 2001 and the presentation of the disorder is variable and mainly consists of a combination of signs common in the elderly~~<ref name="~~PMID19574929~~"><pubmed>19574929</pubmed></ref>.~~ The core clinical symptoms of FXTAS are prominent tremors, [[#Glossary \| '''ataxia''']] and cognitive decline. Cognitive decline occurs in at least 50% of the patients with neurological symptoms usually at a later age (>70 years)~~<ref name="~~PMID21476992~~"><pubmed>21476992</pubmed></ref>.~~		\| valign="top" bgcolor="lavenderblush"\|Hagerman and colleagues first recognized Fragile X-associated tremor/[[#Glossary \| '''ataxia''']] syndrome (FXTAS).{{#pmid:11445641\|PMID11445641}} FXTAS is a disorder that is under-recognized because the first published report was only in 2001 and the presentation of the disorder is variable and mainly consists of a combination of signs common in the elderly.{{#pmid:19574929\|PMID19574929}} The core clinical symptoms of FXTAS are prominent tremors, [[#Glossary \| '''ataxia''']] and cognitive decline. Cognitive decline occurs in at least 50% of the patients with neurological symptoms usually at a later age (>70 years).{{#pmid:21476992\|PMID21476992}}
	\|-		\|-
	\| valign="top" bgcolor="mistyrose"\|'''2010'''		\| valign="top" bgcolor="mistyrose"\|'''2010'''
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	Recent data suggests that Fragile X Syndrome (FXS) approximately affects 1 in 2,500 individuals of which there is approximately equal prevalence in males and females~~<ref name="~~PMID21748281~~"><pubmed>21748281</pubmed></ref>.~~		Recent data suggests that Fragile X Syndrome (FXS) approximately affects 1 in 2,500 individuals of which there is approximately equal prevalence in males and females.{{#pmid:21748281\|PMID21748281}}


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	There are an inadequate number of studies conducted on Fragile X Syndrome of different populations. However, those studies that have been done, suggests that there is a difference in prevalence across populations~~<ref name="~~PMID11545690~~"><pubmed>11545690</pubmed></ref>.~~ For example:		There are an inadequate number of studies conducted on Fragile X Syndrome of different populations. However, those studies that have been done, suggests that there is a difference in prevalence across populations.{{#pmid:11545690\|PMID11545690}} For example:
	* Figures from Israel find the frequency of the premutation carrier state in females to be approximately 1 in 130 and the full mutation to be present in 1 in 2,500 females<ref name="PMID21748281 "/> .		* Figures from Israel find the frequency of the premutation carrier state in females to be approximately 1 in 130 and the full mutation to be present in 1 in 2,500 females<ref name="PMID21748281 "/> .
	*Data from Canada, suggest that the incidence of premutation carriers to be 1 in 800 males and 1 in 260 females<ref name="PMID21748281 "/>.		*Data from Canada, suggest that the incidence of premutation carriers to be 1 in 800 males and 1 in 260 females<ref name="PMID21748281 "/>.
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	* Another study established a lack of large CGG repeats in Native American populations to suggest a lower prevalence of the syndrome amongst this population<ref name="PMID11545690"/>.		* Another study established a lack of large CGG repeats in Native American populations to suggest a lower prevalence of the syndrome amongst this population<ref name="PMID11545690"/>.
	* Similarly, the Spanish Basque population has reported a lower prevalence of males with the FXS of pure Basque origin in a mentally retarded population and a lower frequency of large CGG repeats<ref name="PMID11545690"/>.		* Similarly, the Spanish Basque population has reported a lower prevalence of males with the FXS of pure Basque origin in a mentally retarded population and a lower frequency of large CGG repeats<ref name="PMID11545690"/>.
	* Studies carried out on Indian Fragile X patients have shown a frequency of 7% among the mentally retarded population~~<ref name="~~PMID20090132~~"><pubmed>20090132</pubmed></ref>.~~		* Studies carried out on Indian Fragile X patients have shown a frequency of 7% among the mentally retarded population.{{#pmid:20090132\|PMID20090132}}
	A study in the United States has found variability amongst the frequency of premutation carriers of different ethnicities within their population~~<ref name="~~PMID21116185~~"><pubmed>21116185</pubmed></ref>.~~		A study in the United States has found variability amongst the frequency of premutation carriers of different ethnicities within their population.{{#pmid:21116185\|PMID21116185}}
	* Caucasian Americans had a frequency of 1 in 169<ref name="PMID21116185"/>		* Caucasian Americans had a frequency of 1 in 169<ref name="PMID21116185"/>
	* Hispanics had a frequency of 1 in 287<ref name="PMID21116185"/>		* Hispanics had a frequency of 1 in 287<ref name="PMID21116185"/>
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	* '''Premutation amplification''' refers to repeats between 61-200. While children born with premutation amplification are largely [[#Glossary \| '''asymptomatic''']], studies have shown that it predisposes to Parkinson's disease, intention tremor and brain [[#Glossary \| '''atrophy''']], as well as ovarian failure in women~~<ref><pubmed>~~10208170~~</pubmed></ref><ref><pubmed>~~11445641~~</pubmed></ref><ref><pubmed>~~12638084~~</pubmed></ref>.~~		* '''Premutation amplification''' refers to repeats between 61-200. While children born with premutation amplification are largely [[#Glossary \| '''asymptomatic''']], studies have shown that it predisposes to Parkinson's disease, intention tremor and brain [[#Glossary \| '''atrophy''']], as well as ovarian failure in women.{{#pmid:10208170\|PMID10208170}}{{#pmid:11445641\|PMID11445641}}{{#pmid:12638084\|PMID12638084}}

	[[File:Fragile site appearance and distribution.jpg\|thumb\|200px\|thumb\|Fragile site appearance and distribution]]		[[File:Fragile site appearance and distribution.jpg\|thumb\|200px\|thumb\|Fragile site appearance and distribution]]
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	Elongation of the FMR1 gene beyond 200 repeats results in [[#Glossary \| '''methylation''']] of the CpG island that typically regulates its [[#Glossary \| '''expression''']], the loss of which inhibits the binding of [[#Glossary \| '''transcription factors''']], effectively [[#Glossary \| '''silencing''']] the gene and causing fragile X mental retardation protein 1 (FMRP) to be under-expressed. [[#Glossary \| '''Transcription''']] is similarly inhibited by [[#Glossary \| '''methylation''']]-induced [[#Glossary \| '''chromatin''']] condensation~~<ref><pubmed>~~17477822~~</pubmed></ref>.~~ Repression of FMRP expression interferes with nervous system functioning<ref>http://ghr.nlm.nih.gov/condition/fragile-x-syndrome</ref>. Studies have also suggested FMRP playing a role in synapse formation and function~~<ref><pubmed>~~12052912~~</pubmed></ref><ref><pubmed>~~18054394~~</pubmed></ref>~~, being significantly expressed in the brain and testes~~<ref><pubmed>~~8401578~~</pubmed></ref>.~~ The prominence of FMR1 mRNA in the normal developing fetal central and peripheral nervous systems strongly suggests that its absence brings about the mental retardation typical of sufferers of the disease~~<ref><pubmed>~~8348153~~</pubmed></ref>.~~ FMRP itself has been found to play a role in [[#Glossary \|'''synaptic plasticity''']] via its deactivation of gene expression by forming a complex with a RISC subunit containing Dicer enzyme~~<ref><pubmed>~~12368260~~</pubmed></ref><ref><pubmed>~~12368261~~</pubmed></ref>.~~ Its role in RNA metabolism sees FMRP repressing translation of mRNA at synapses via interaction with proteins required for miRNA function~~<ref><pubmed>~~17178403~~</pubmed></ref>.~~		Elongation of the FMR1 gene beyond 200 repeats results in [[#Glossary \| '''methylation''']] of the CpG island that typically regulates its [[#Glossary \| '''expression''']], the loss of which inhibits the binding of [[#Glossary \| '''transcription factors''']], effectively [[#Glossary \| '''silencing''']] the gene and causing fragile X mental retardation protein 1 (FMRP) to be under-expressed. [[#Glossary \| '''Transcription''']] is similarly inhibited by [[#Glossary \| '''methylation''']]-induced [[#Glossary \| '''chromatin''']] condensation.{{#pmid:17477822\|PMID17477822}} Repression of FMRP expression interferes with nervous system functioning<ref>http://ghr.nlm.nih.gov/condition/fragile-x-syndrome</ref>. Studies have also suggested FMRP playing a role in synapse formation and function{{#pmid:12052912\|PMID12052912}}{{#pmid:18054394\|PMID18054394}}, being significantly expressed in the brain and testes.{{#pmid:8401578\|PMID8401578}} The prominence of FMR1 mRNA in the normal developing fetal central and peripheral nervous systems strongly suggests that its absence brings about the mental retardation typical of sufferers of the disease.{{#pmid:8348153\|PMID8348153}} FMRP itself has been found to play a role in [[#Glossary \|'''synaptic plasticity''']] via its deactivation of gene expression by forming a complex with a RISC subunit containing Dicer enzyme.{{#pmid:12368260\|PMID12368260}}{{#pmid:12368261\|PMID12368261}} Its role in RNA metabolism sees FMRP repressing translation of mRNA at synapses via interaction with proteins required for miRNA function.{{#pmid:17178403\|PMID17178403}}