Expansion mutation frequency and CGG/GCC repeat polymorphism in FMR1 and FMR2 genes in an Indian population

Based on molecular screening, we estimated the frequencies of fragile X syn drome and FRAXE syndrome in an institutionalized population (n = 130) in Ne w Delhi, India. Eligibility criteria for inclusion of subjects in the study were mild/moderate mental retardation, with/without family history, and th e fragile X clinical phenotype. Screening by Southern hybridization reveale d an overall frequency of 0.077 of the syndrome in the sample population Th e disorder was observed with a high frequency (0.1) among males as compared to females (0.027). No expansions of FMR2 allele were observed in the same study sample. CGG/ GCC allelic polymorphism of FMR1 and FMR2 were establis hed from a total of 392 X chromosomes, using the radioactive polymerase cha in reaction-polyacrylamide gel electrophoresis method. Distinct repeat size s, repeat ranges, and repeat modes characterised the FMR1 and FMR2 alleles. In the X chromosomes of both MR individuals and unaffected controls, unimo dal values of 29 and 15 repeats in FMR1 and FMR2 genes, respectively, were observed. Allele frequency distribution was symmetrical at the FMR1 locus w hereas a significant positive skew was observed for the FMR2 alleles. The o bserved heterozygosity of the FMR1 gene was 0.772 compared to 0.839 of FMR2 ; Correlation of CGG/ GCC repeats of FMR1 and FMR2 did not show any associa tion of repeat sizes at these two loci (correlation coefficient, rho = 0.09 ). CGG/GCC repeat variation at FMR1 and FMR2 loci observed in this study sa mple are different from that reported for the other Caucasian and Asian pop ulations. Genet. Epidemiol. 20:129-144, 2001. (C) 2001 Wiley-Liss, Inc.