A nonsense mutation in FMR1 causing fragile X syndrome

Karen Gronskov (1) , Karen Brøndum-Nielsen (1) , Alma Dedic (1) , Helle Hjalgrim (1)

1 Medical Genetics Laboratory

Fragile X syndrome is a common cause of inherited intellectual disability. It is caused by lack of the FMR1 gene product FMRP. Fragile X syndrome is a common cause of inherited intellectual disability. It is caused by lack of the FMR1 gene product FMRP. The most frequent cause is an expansion of a CGG repeat located in the 5' UTR of FMR1. Alleles with 200 or more repeats become hypermethylated and transcriptionally silent. Only few patients with intragenic point mutations in FMR1 have been reported and to-day routine analysis of patients referred for fragile X syndrome includes solely analysis for repeat expansion and methylation status. We identified a substitution in exon 2 of FMR1, c.80C>A, causing a nonsense mutation p.Ser27X, in a patient with classical clinical symptoms of fragile X syndrome. The mother who carried the mutation in heterozygous form presented with mild intellectual impairment. We conclude that further studies including Western blot and DNA sequence analysis of the FMR1 gene should be performed in patients with typical symptoms of fragile X syndrome, in whom no CGG repeat expansion is detected.

Mots clés: fragile X syndrome; nonsense mutation; mental retardation

Karen Gronskov, Karen Brøndum-Nielsen, Alma Dedic, Helle Hjalgrim. A nonsense mutation in FMR1 causing fragile X syndrome. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.223⟩. ⟨hal-00602294⟩