Fragile X syndrome is the most frequent hereditary cause of mental retardation after Down syndrome. Expansion of CGG repeats in the 5¢ UTR of the fragile X mental retardation gene 1 (FMR1) causes gene inactivation in most of the cases. The FMR1 gene is classified into normal 5-44; gray zone 45-54; premutation 55 to < 200; and full mutation ‡ 200 repeats. Precise sizing of FMR1 alleles is important to understand their variation, predisposition, and for genetic counseling. Meta-analysis reveals prevalence of premutation carriers as 1 in 259. No such reports are available in India. About 705 women from Tamil Nadu, South India, were screened for the FMR1 allelic variation by using radioactive polymerase chain reaction-polyacrylamide gel electrophoresis (PAGE) analysis. The women who were homozygous by radioactive polymerase chain reaction (rPCR) were reanalyzed by methylation-specific polymerase chain reaction (Ms-PCR) and GeneScan analysis. The techniques were validated and compared to arrive at a correction factor. Among 122 genotypes, 35 repeat variants ranging in size from 16 to 57 were observed. The most common repeat is 30 followed by 29. One in 353 women carried the premutation. No full mutations were observed. Screening populations with low frequency of premutations may not be applicable. Ms-PCR is more suitable for routine screening and clinical testing compared with rPCR-PAGE analysis.

No abstract

Fragile X syndrome is the most common genetic cause of intellectual disability (ID) and is also well known to have a role in primary ovarian insufficiency (POI) and fragile X‐associated tremor ataxia syndrome (FXTAS) that expresses across generations. The objective was to compare the CGG repeat variants in FMR1 gene among three correlating cohorts of ID, autism and idiopathic POI. Thirty‐six patients with ID, 12 with autism spectrum disorder (ASD) and 13 females with idiopathic POI were screened for FMR1 CGG repeat size by fluorescent methylation‐specific PCR and GeneScan analysis, irrespective of Hagerman checklist clinical scores. Among 29 males and seven females, 11 FMR1 allelic variants ranging from 21 to >200 CGG repeats were observed. Three (CF2‐3, 39‐5, 44‐2) out of 29 males had full mutation alleles accounting for a 10.34% incidence of FXS among idiopathic ID males. One of them was a mosaic for CGG repeats with both premutation and full mutation alleles. The frequency of fragile X syndrome is high among patients with idiopathic ID; they also had a high score for the clinical check list. A cascade testing that begins with checklist evaluation prior to DNA analysis will be cost‐effective for establishing early diagnosis in South India. With the huge disease burden, there is a need for the establishment of more molecular diagnostics and self‐help groups for fragile X syndrome.

No abstract

No abstract