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 inher ited mental retardation, is caused by abnormal expansion of the CGG trinucl eotide repeats in the 5' untranslated region of the FMR-1 gene. In this stu dy, we describe the prenatal diagnosis of fragile X syndrome and the distri bution of CGG repeat numbers in the FMR-1 gene, which has not been previous ly 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 chromoso mes) and 349 mentally retarded patients (429 X chromosomes). For prenatal d iagnosis 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 distribu tion of the (CGG)(n) alleles between the mentally retarded and normal subje cts, the data were pooled. Among the 779 X chromosomes studied, 24 differen t alleles were identified with a low of 16 and a high of 45 CGG repeats. Th e 29 repeat allele was the most common, followed by the 30 and the 28 repea t alleles. We effectively amplified slightly expanded premutation alleles o f up to about 90 CGG repeats. In the prenatally diagnosed fetus, a normal 2 9 repeat allele was found. Conclusions: Determination of the distribution of the CGG repeats in the FM R-1 gene in Taiwanese is useful in genetic counseling regarding fragile X s yndrome. Prenatal molecular diagnosis of the syndrome can be successfully p erformed using amniotic fluid cells.