ABSTRACT
Fragile X syndrome (FRAXA) is the most common form of inherited mental retardation (MR). The mutational mechanism leading to the disease involves an expansion of a trinucleotide repeat located at the 5' UTR region of the gene FMR-1. Four types of alleles can be identified in the population, based on the number of repeats: normal (6-40), gray-zone (41-60), premutated (61-200), and fully mutated (>200). Despite only full mutations being associated with the development of the disorder, some authors propose a correlation between FRAXA premutation and the occurrence of premature ovarian failure (POF). We have undertaken a study in 58 women from 24 fragile X syndrome families ascertained for FRAXA testing. Using Southern blotting for direct DNA analysis we have identified 19 normal, 33 premutation carriers, and 6 fully mutated individuals (including 4 somatic mosaics showing premutated and fully mutated alleles). Among the premutated women, 11 experienced menopause before the age of 40 (POF), including one somatic mosaic, which was different from the ones with normal pattern who did not experience POF. Our data corroborate the notion that females carrying alleles in the premutation range are at high risk of experiencing POF.
Subject(s)
Chromosome Segregation , Chromosomes, Human, X/genetics , Fragile X Syndrome/genetics , Nerve Tissue Proteins/genetics , Primary Ovarian Insufficiency/genetics , RNA-Binding Proteins , Adolescent , Adult , Aged , Alleles , Brazil , Child , Female , Fragile X Mental Retardation Protein , Gene Silencing , Humans , Male , Middle Aged , Pedigree , Trinucleotide Repeat ExpansionABSTRACT
A síndrome do X frágil é a causa mais comum de retardo mental herdado; entretanto, é subdiagnosticada na populaçäo pediátrica. Objetivamos, neste estudo, determinar as características clínicas pré e pós-puberais mais significativas observadas entre indivíduos que apresentam a mutaçäo no gene FMR-1, e que possam ser utilizadas como método de triagem dos pacientes que devem ser submetidos à análise molecular. A partir de protocolo clínico-laboratorial, foram analisados 104 indivíduos (92 do gênero masculino e 12 do feminino) portadores de retardo mental idiopático. 17 pacientes (14 do gênero masculino) apresentaram a mutaçäo completa. História familiar de retardo mental e contato ocular pobre foram os achados que se mostraram associados, de forma estatisticamente significante (p<0,05), aos pacientes com a síndrome do X frágil em idade pré e pós-puberal. Os pacientes em idade pós-puberal também diferiram dos controles em relaçäo à presença de orelhas grandes, fronte proeminente e macroorquidismo
