Atypical finding of fragile x syndrome in a family with a female index case and no mentally retarded male

Abstract

Fragile X Syndrome (X-fra) is the most common cause of inherited Mental Retardation (MR) and one of the most common genetic diseases (l). The main mutation that produces this syndrome is the anomalous expansion of a triplet (CGG) within the FMR-1 gene in the Xq28 region of the X chromosome. The transmission of this affectation is complex: initially considered as X-linked recessive (affected males and transmitting women), it soon became known that there were women who had MR to a greater or lesser degree, which is now considered a dominant disease with incomplete penetrance. Furthermore, the expansion takes place in two stages: a first in which the number of repetitions of the CGG triplet does not exceed 200 and which is called "Premutation", in which both women and men are transmitters with normal intelligence; and a second stage called "Complete Mutation", with more than 200 repetitions, in which all men present MR, while women suffer it in approximately 59% Pl. The most common is that these women with the syndrome are diagnosed from a first male index case with MRI, subsequently studying the family. Thus, for example, in our Genetics Unit, X-fra is routinely checked in all men with unknown MRI who come to our laboratory and, however, women with mental deficits are only studied for X-fra by request. of some clinicians under suspicion of the syndrome (suggestive phenotype, family history, etc.)