Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families
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- 15 April 2009
- journal article
- Published by Springer Science and Business Media LLC in European Journal of Human Genetics
- Vol. 17 (10), 1359-1362
- https://doi.org/10.1038/ejhg.2009.51
Abstract
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 ~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.This publication has 27 references indexed in Scilit:
- Expanded clinical phenotype of women with the FMR1 premutationAmerican Journal of Medical Genetics Part A, 2008
- Evidence for, and a spectrum of, neurological involvement in carriers of the fragile X pre‐mutation: FXTAS and beyondClinical Genetics, 2005
- Incidence of Fragile X in 5,000 Consecutive Newborn MalesGenetic Testing, 2003
- Premutation and intermediate-size FMR1 alleles in 10 572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome allelesHuman Molecular Genetics, 2002
- Neurobehavioral phenotype in carriers of the fragile X premutationAmerican Journal of Medical Genetics, 2001
- Elevated Levels of FMR1 mRNA in Carrier Males: A New Mechanism of Involvement in the Fragile-X SyndromeAmerican Journal of Human Genetics, 2000
- Fragile X premutation is a significant risk factor for premature ovarian failure: The international collaborative POF in fragile X study?preliminary dataAmerican Journal of Medical Genetics, 1999
- The prevalence and characteristics of fibromyalgia in the general populationArthritis & Rheumatism, 1995
- Hypothalamic–pituitary–adrenal axis perturbations in patients with fibromyalgiaArthritis & Rheumatism, 1994
- Heterozygous fragile X female: Historical, physical, cognitive, and cytogenetic featuresAmerican Journal of Medical Genetics, 1991