A novel duplication in the FMR1 gene: Implications for molecular analysis in fragile X syndrome and repeat instability

Department of Chemistry, University of Turku, Turku, Southwest Finland, Finland
Clinical Genetics (Impact Factor: 3.93). 01/2008; 72(6):528-31. DOI: 10.1111/j.1399-0004.2007.00903.x
Source: PubMed


We have observed a 49 bp tandem duplication adjacent to the triplet repeat of the FMR1 gene and have shown it to occur as a variant in Finland. It affects the primers commonly used in molecular analysis of fragile X syndrome by polymerase chain reaction (PCR) methods. One concern is that females with the full mutation and variant alleles might be missed because of the two PCR products generated by the variant. We suggest that the duplication has arisen by a misalignment of the proximal end of the repeat tract and the non-adjacent GGCGGCGGCGG-sequence located 37 bp upstream and may indicate a mutation hot spot. The discovery of this duplication and the previous observations on deletions associated with full mutations in FMR1 indicate that realignment between the repeat tract and dispersed non-adjacent homologous repetitive sequences may also play a role in repeat instability in fragile X.

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