Fragile X Syndrome: Difference between revisions
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| [[File:Fragile X protein cartoon.jpg|600px|alt=Fragile X protein model of function in neurons]] | | [[File:Fragile X protein cartoon.jpg|600px|alt=Fragile X protein model of function in neurons]] | ||
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| FMRP Model<ref name = PMID24204304/> | | '''FMRP Localization in Neurons Model'''<ref name = PMID24204304<pubmed>24204304</pubmed>| [http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003890 PLoS Genet.]</ref> | ||
Alternative splicing of the primary FMRP transcripts generates either ISO6 FMRP lacking the CRD domain, or ISO1 FMRP containing both NLS and CRD domains. | Alternative splicing of the primary FMRP transcripts generates either ISO6 FMRP lacking the CRD domain, or ISO1 FMRP containing both NLS and CRD domains. |
Revision as of 10:53, 15 August 2014
Embryology - 16 Jun 2024 Expand to Translate |
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Introduction
ICD: Q99.2 Fragile X chromosome Fragile X syndrome
Fragile X Syndrome (Mental Retardation, X-linked, associated with marXq28, X-linked mental retardation and macroorchidism, Marker X syndrome, Martin-Bell syndrome).
Fragile X Syndrome (FXS) is the most common form of inherited mental retardation and autism. The condition is caused by a loss of the functional fragile X mental retardation protein (FMRP) an RNA-binding protein that can regulate the translation of specific mRNAs. There are several suggested additional roles for this protein including synaptic development and function[1] and in adult neurogenesis.[2]
The normal FMR1 functional gene can contain a trinucleotide sequence (CGG) repeated between 6 to 44 times. Expansion of this sequence (55 to 200 repeats) in an unmethylated form that generates an unstable sequence. This leads to repression of FMR1 transcription and subsequent decreased protein levels in the brain.
- 2014 - Fragile X Association of Australia Fund raiser Manly Wharf Bridge to Beach Paddle race
- 2011 - Undergraduate Science students project Fragile X Syndrome.
- Links: Neural Abnormalities | Neural System Development | 2011 Student Project - Fragile X Syndrome | Fragile X Association of Australia
Some Recent Findings
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More recent papers |
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Fragile X Syndrome <pubmed limit=5>Fragile X Syndrome</pubmed> |
International Classification of Diseases
The International Classification of Diseases (ICD) World Health Organization's classification used worldwide as the standard diagnostic tool for epidemiology, health management and clinical purposes. This includes the analysis of the general health situation of population groups. It is used to monitor the incidence and prevalence of diseases and other health problems. Within this classification "congenital malformations, deformations and chromosomal abnormalities" are (Q00-Q99) but excludes "inborn errors of metabolism" (E70-E90).
Q99 Other chromosome abnormalities, not elsewhere classified
- Q99.2 Fragile X chromosome Fragile X syndrome
Fragile X-associated Tremor
(Ataxia Syndrome) A mainly male adult-onset condition that causes tremor and affects balance and memory in some "carriers" of the Fragile X gene. Because of the adult onset, this can be mistaken for a range of other neurological disorders including Parkinson's and Alzheimer's disease.
Screening
Screening By Country
- USA - Practice Guidelines of the National Society of Genetic Counselors - original version (2000), updated (2005)[8], latest version (2012)[6].
FMRP and Cajal bodies
A recent study has identified specific isoforms of the Fragile X protein (ISO6 and ISO12) are localised to the nuclear Cajal bodies.[5] The authors have postulated a model (shown below) for these specific function in neurons.
FMRP Localization in Neurons Model[5]
Alternative splicing of the primary FMRP transcripts generates either ISO6 FMRP lacking the CRD domain, or ISO1 FMRP containing both NLS and CRD domains.
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Mouse Model
A Mouse Model of the Human Fragile X Syndrome I304N Mutation[9]
- "The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA-binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5'UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1) in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N) in the second FMRP KH-type RNA-binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1-null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder."
References
- ↑ <pubmed>18957214</pubmed>
- ↑ <pubmed>20386739</pubmed>
- ↑ 3.0 3.1 <pubmed>24523898</pubmed>| PLoS One.
- ↑ <pubmed>24528851</pubmed>
- ↑ 5.0 5.1 5.2 24204304</pubmed>| PLoS Genet.
- ↑ 6.0 6.1 <pubmed>22797890</pubmed>
- ↑ <pubmed>22750206</pubmed>
- ↑ <pubmed>16047089</pubmed>
- ↑ <pubmed>20011099</pubmed>| PMC2779495 | PLoS Genet.
NCBI Bookshelf
- Clinical Methods 3rd ed. Walker, H.K.; Hall, W.D.; Hurst, J.W.; editors Stoneham (MA): Butterworth Publishers; c1990 Table - Recognizable Genetic Conditions
- Modern Genetic Analysis Griffiths, Anthony J.F.; Gelbart, William M.; Miller, Jeffrey H.; Lewontin, Richard C. New York: W. H. Freeman & Co.; c1999.
- Introduction to Genetic Analysis 7th ed. Griffiths, Anthony J.F.; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. New York: W. H. Freeman & Co.; c1999.
Reviews
<pubmed>24415997</pubmed> <pubmed>22482801</pubmed> <pubmed>22395002</pubmed> <pubmed>21934270 </pubmed> <pubmed>21893938</pubmed> <pubmed>21518720</pubmed> <pubmed>21090964</pubmed>
Articles
<pubmed></pubmed> <pubmed></pubmed> <pubmed></pubmed> <pubmed>24354947</pubmed>
Books
Note: books are listed for educational and information purposes only and does not suggest a commercial product endorsement.
OMIM
Search PubMed
Search PubMed Now: Fragile X Syndrome
External Links
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- Australia - Fragile X Association of Australia
- USA - National Society of Genetic Counselors | National Fragile X Foundation
Glossary Links
- Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link
Cite this page: Hill, M.A. (2024, June 16) Embryology Fragile X Syndrome. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Fragile_X_Syndrome
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G