2. Academic Validation
  3. Fragile X syndrome due to a missense mutation

Fragile X syndrome due to a missense mutation

  • Eur J Hum Genet. 2014 Oct;22(10):1185-9. doi: 10.1038/ejhg.2013.311.
Leila K Myrick 1,  Mika Nakamoto-Kinoshita 1,  Noralane M Lindor 2,  Salman Kirmani 3,  Xiaodong Cheng 4,  Stephen T Warren 5
Affiliations

Affiliations

  • 1 Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
  • 2 Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA.
  • 3 Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA.
  • 4 Department of Biochemistry, Emory University, Atlanta, GA, USA.
  • 5 1] Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA [2] Department of Biochemistry, Emory University, Atlanta, GA, USA [3] Department of Pediatrics, Emory University, Atlanta, GA, USA.
PMID: 24448548 DOI: 10.1038/ejhg.2013.311
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.

Figures