Penetrance of FMR1 premutation associated pathologies in fragile X syndrome families
Por:
Rodriguez-Revenga, L, Madrigal, I, Pagonabarraga, J, Xuncla, M, Badenas, C, Kulisevsky, J, Gomez, B, Mila, M
Publicada:
1 oct 2009
Resumen:
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 B20% 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. European Journal of Human Genetics (2009) 17, 1359-1362; doi: 10.1038/ejhg.2009.51; published online 15 April 2009
Filiaciones:
Rodriguez-Revenga, L:
CIBERER, Barcelona, Spain
Madrigal, I:
CIBERER, Barcelona, Spain
Pagonabarraga, J:
Autonomous Univ Barcelona, Movement Disorders Unit, Dept Neurol, Sant Pau Hosp, E-08193 Barcelona, Spain
CIBERNED, Barcelona, Spain
Xuncla, M:
Fundacio Clin Recerca Biomed, Barcelona, Spain
Badenas, C:
CIBERER, Barcelona, Spain
IDIBAPS, Barcelona, Spain
Kulisevsky, J:
Autonomous Univ Barcelona, Movement Disorders Unit, Dept Neurol, Sant Pau Hosp, E-08193 Barcelona, Spain
CIBERNED, Barcelona, Spain
Gomez, B:
CDI Hosp Sant Pau, Dept Radiol, Barcelona, Spain
Mila, M:
Hosp Clin Barcelona, Biochem & Mol Genet Serv, Dept Biochem & Mol Genet, Barcelona 08036, Spain
CIBERER, Barcelona, Spain
IDIBAPS, Barcelona, Spain
Green Published, Bronze
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