The Fragile X syndrome in patients with mental retardation of unknown cause in Mexico

Abstract

The Fragile X syndrome (Fra-X) is characterized by mental retardation, macroorchidism and characteristic facial features, it is associated with the folate sensitive fragile site FRAXA at Xq27.3 The disease results from lack of expression of the FMR1 gene and in the vast majority of cases the mutation is an expansion of a CGG trinucleotide repeat localized in the 5 untranslated region. In the National Institute of Pediatrics in Mexico City, there are many patients who are considered to have mental retardation of unknown cause (MRUC) after a multidisciplinary and exhaustive study. Some of them have clinical manifestations of Fra-X, although in 25 years, diagnosis has been confirmed with cytogenetic study in only five cases. This may be was due to a low frequency of Fra-X in our population or to a misdiagnosis because molecular techniques were not previously available.The purpose of this paper was to establish the frequency of Fra-X in a group of patients with MRUC by the molecular analysis of the FMR-1 gene.Forty pediarric patients of both sexes and their first-degree relatives were included. The CGG trinucleotides were analyzed with PCR and Southern blot. Two of our patients had an expansion of the trinucleotides and it was interesting that one of them had not somatic alterations of the disease and mental retardation was the unique clinical manifestation of Fra-X. We demonstrated by Southern blot that both mothers had a premutation and the brother of one of the index cases was also affected. In our cases two patients had a family history and clinical manifestations which strongly suggested Fra-X but it was not corroborated with this molecular study. Our results confirm that the molecular analysis of the FMR-1 gene is necessary for a correct diagnosis of Fra-X and suggest that this disease is the cause of mental retardation in 5% of the patients considered to have MRUC in our population. Partial supported by CONACYT: A. Gonzaacute;lez-del Angel 90158.