Document Detail


Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families.
MedLine Citation:
PMID:  19367323     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Within the past few years, there has been a significant change in identifying and characterizing the FMR1 premutation associated phenotypes. The premutation has been associated with elevated FMR1 mRNA levels and slight to moderate reductions in FMRP levels. Furthermore, it has been established that approximately 20% of female premutation carriers present primary ovarian insufficiency (POI) and that fragile X-associated tremor/ataxia syndrome (FXTAS) occurs in one-third of all male premutation carriers older than 50 years. Besides POI and FXTAS, new disorders have recently been described among individuals (especially females) with the FMR1 premutation. Those pathologies include thyroid disease, hypertension, seizures, peripheral neuropathy, and fibromyalgia. However there are few reports related to FXTAS penetrance among female premutation carriers or regarding these disorders recently associated to the FMR1 premutation. Therefore, we have evaluated 398 fragile X syndrome (FXS) families in an attempt to provide an estimation of the premutation associated phenotypes penetrance. Our results show that signs of FXTAS are detected in 16.5% of female premutation carriers and in 45.5% of premutated males older than 50 years. Furthermore, among females with the FMR1 premutation, penetrance of POI, thyroid disease and chronic muscle pain is 18.6, 15.9 and 24.4%, respectively. The knowledge of this data might be useful for accurate genetic counselling as well as for a better characterization of the clinical phenotypes of FMR1 premutation carriers.
Authors:
Laia Rodriguez-Revenga; Irene Madrigal; Javier Pagonabarraga; Mar Xunclà; Celia Badenas; Jaime Kulisevsky; Beatriz Gomez; Montserrat Milà
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-15
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  17     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-24     Completed Date:  2009-12-14     Revised Date:  2010-12-17    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  1359-62     Citation Subset:  IM    
Affiliation:
CIBER de Enfermedades Raras, Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged, 80 and over
Family Health
Female
Fragile X Mental Retardation Protein / genetics*
Fragile X Syndrome / genetics*
Genetic Predisposition to Disease*
Humans
Male
Middle Aged
Models, Genetic
Mutation*
Ovarian Diseases / genetics
Phenotype
RNA, Messenger / metabolism
Chemical
Reg. No./Substance:
0/FMR1 protein, human; 0/RNA, Messenger; 139135-51-6/Fragile X Mental Retardation Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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