Molecular diagnosis of fragile X syndrome and distribution of CGG repeats in the FMR-1 gene in Taiwanese

Background and purpose: Fragile X syndrome, the most frequent form of inherited mental retardation, is caused by abnormal expansion of the CGG trinucleotide repeats in the 5' untranslated region of the FMR-1 gene. In this study, we describe the prenatal diagnosis of fragile X syndrome and the distribution of CGG repeat numbers in the FMR-1 gene, which has not been previously reported in Taiwanese. Methods: Using polymerase chain reaction (PCR), we determined the range of the CGG repeats in the FMR-1 gene in 316 normal individuals (350 X chromosomes) and 349 mentally retarded patients (499 X chromosomes). For prenatal diagnosis of fragile X syndrome, DNA extracted from amniotic fluid cells was used for PCR determination of CGG repeats. Results: Because there were no significant differences between the distribution of the (CGG)[n] alleles between the mentally retarded and normal subjects, the data were pooled. Among the 779 X chromosomes studied, 24 different alleles were identified with a low of 16 and a high of 45 CGG repeats. The 29 repeat allele was the most common, followed by the 30 and the 28 repeat alleles. We effectively amplified slightly expanded premutation alleles of up to about 90 CGG repeats. In the prenatally diagnosed fetus, a normal 29 repeat allele was found. Conclusions: Determination of the distribution of the CGG repeats in the FMR-1 gene in Taiwanese is useful in genetic counseling regarding fragile X syndrome. Prenatal molecular diagnosis of the syndrome can be successfully performed using amniotic fluid cells.