Stability of the FMR1 CGG repeat in a Basque sample.

The fragile X syndrome is an X-chromosome-linked dominant disorder with reduced penetrance. It is the most common inherited form of mental retardation. The molecular basis is usually the unstable expansion of a CGG trinucleotide repeat in the 5' untranslated region of the first exon of the FMR1 gene, which resides at chromosome position Xq27.3 and is coincident with the cytogenetic fragile site FRAXA , which characterizes the syndrome. In the Biscay province of the Basque Country the prevalence of FRAXA in a mentally retarded sample of nonBasque origin is in the range of other analyzed Spanish populations. In the sample of Basque origin we have not found FRAXA site expression and the repeat size is in the normal range. Based on this, we have examined FMR1 gene stability in normal individuals of Basque origin from the Biscay province. This study is based on a sample of 242 X chromosomes. The results from the CGG repeat region of FMR1 indicate that a prevalence of predisposing normal alleles toward repeat instability in the Basque population is 0.00% or near to it. This could be 1 of the explanations of the apparently low fragile X syndrome incidence found in the Basque mentally retarded sample analyzed by us. This low incidence does not seem to be associated with the flanking microsatellite markers. Since the early 1900s an excess of males has been noted among mentally retarded persons. Studies of many family pedigrees suggest that a sex-linked mode of transmission is involved in certain cases of mental retardation. In 1969 the fragile X site, located on the long arm of the X chromosome in the subband Xq27.3 (FRAXA), was described (Lubs 1969). Several years after its recognition, the fragile X site was determined to be associated with X-chromosome-linked mental retardation in several families and was believed to be responsible for the condition that had been called Martin-Bell syndrome 1 Departamento de Biologia Animal y Genetica, Facultad de Ciencias, Universidad del Pais Vasco, Apartado 644, 48080 Bilbao, Spain. 2 Instituto de Patologia e Imunologia Molecular, Universidad do Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, 4200 Porto, Portugal. 3 Instituto Superior da Maia, S. Pedro Avioso, Castelo Maia 4470, Portugal. Human Biology, February 1999, v. 71, no. 1, pp. 55-68. Copyright © 1999 Wayne State University Press, Detroit, Michigan 48201-1309