ABSTRACT
Fragile X syndrome is the most common form of inherited mental retardation in men. The molecular mechanism underlying the disease is an amplification of a polymorphic trinucleotide repeat (CGG)n located at 5' end of FMR1 which promotes transcriptional silencing of the gene. Four different classes of alleles could be distinguished in the population based on the size of the repeat, however only large amplifications over 200 CGG are associated with the disease. In the past decade several authors have associated premutated alleles, which harbor expansions from 61 to 200 repeats, with the occurrence of premature ovarian failure (POF). In this work we describe a large Brazilian family in which a POF/premutated woman has transmitted to five out of seven daughters a FMR1 premutated allele. From these five women with premutations, three have experienced premature ovarian failure. Our data clearly indicate a co-segregation pattern of inheritance between POF and fragile X premutation.
Subject(s)
Chromosome Segregation , Chromosomes, Human, X/genetics , Nerve Tissue Proteins/genetics , Primary Ovarian Insufficiency/genetics , RNA-Binding Proteins , Adult , Alleles , Brazil , Female , Fragile X Mental Retardation Protein , Gene Silencing , Humans , Male , Pedigree , Trinucleotide RepeatsABSTRACT
Neste estudo investigamos a organizaçäo cromossômica de pacientes com retardo mental e/ou malformaçöes congênitas, visando a avaliaçäo de causas genéticas associadas a estes distúrbios. Os padröes de bandas GTG e CBG foram estudados a partir da cultura de linfócitos de sangue periférico, estimulados por fitohemaglutinina M. Dentre os 98 indivíduos portadores de retardo mental e/ou malformaçöes congênitas analisados, diagnosticamos as seguintes síndromes: 12 casos de Down, dois de Edwards, um de Patau, cinco de Turner, dois de Klinefelter, um de "cri-du-chat", e um caso de translocaçäo balanceada entre os cromossomos 13 e 14, um caso de cromossomo derivado e um outro de cromossomo marcador. Encontramos anomalias cromossômicas em 26 por cento dos pacientes, das quais 82 por cento eram alteraçöes numéricas e o restante (18 por cento) representou rearranjos estruturais. Este percentual significativo enfatiza o uso da cariotipagem de rotina em pacientes com retardo mental e/ou malformaçöes congênitas.
