Mutational analyses of the FMR1 gene in Chinese pediatric population of fragile x suspects: low tolerance for point mutation.

CGG repeat expansion is the most common cause of fragile X syndrome. Numerous efforts have been made to identify novel mutations in patients with intellectual disability, developmental delay, and/or autism. To evaluate the mutational spectrum in the at-risk Chinese population, 60 pediatric patients presenting fragile X traits but normal-sized CGG repeats were sequenced for all 17 exons and regulatory regions in FMR1. A c.879A>C mutation, reported to alter a neighboring splicing, was detected in a severely retarded male and his normal mother. However, the exon junction appears unaffected. A 237-kb deletion covering the entire FMR1 was identified to cause moderate intellectual disability and marked hyperactivity in an 8-year-old boy. The 5' and 3' breakpoints were buried in the surrounding long interspersed and short interspersed elements, respectively. In general, missense mutations do not commonly cause fragile X syndrome, whereas deletions should be considered with caution in patient referrals presenting with developmental delay and/or ordinary retardation.