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Fragile X syndrome due to a missense mutation.

ABSTRACT: Fragile X syndrome is a common inherited form of intellectual disability and autism spectrum disorder. Most patients exhibit a massive CGG-repeat expansion mutation in the FMR1 gene that silences the locus. In over two decades since the discovery of FMR1, only a single missense mutation (p.(Ile304Asn)) has been reported as causing fragile X syndrome. Here we describe a 16-year-old male presenting with fragile X syndrome but without the repeat expansion mutation. Rather, we find a missense mutation, c.797G>A, that replaces glycine 266 with glutamic acid (p.(Gly266Glu)). The Gly266Glu FMR protein abolished many functional properties of the protein. This patient highlights the diagnostic utility of FMR1 sequencing.

SUBMITTER: Myrick LK

PROVIDER: S-EPMC4169535 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Fragile X syndrome due to a missense mutation.

Myrick Leila K LK Nakamoto-Kinoshita Mika M Lindor Noralane M NM Kirmani Salman S Cheng Xiaodong X Warren Stephen T ST

European journal of human genetics : EJHG 20140122 10

Fragile X syndrome is a common inherited form of intellectual disability and autism spectrum disorder. Most patients exhibit a massive CGG-repeat expansion mutation in the FMR1 gene that silences the locus. In over two decades since the discovery of FMR1, only a single missense mutation (p.(Ile304Asn)) has been reported as causing fragile X syndrome. Here we describe a 16-year-old male presenting with fragile X syndrome but without the repeat expansion mutation. Rather, we find a missense mutati ...[more]

PMID: 24448548

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