Fragile X syndrome due to a missense mutation.
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.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Leila K
LK
Myrick
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Mika
M
Nakamoto-Kinoshita
Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA.
Noralane M
NM
Lindor
Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA.
Salman
S
Kirmani
Department of Biochemistry, Emory University, Atlanta, GA, USA.
Xiaodong
X
Cheng
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.
Stephen T
ST
Warren
D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics*; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D019680:Trinucleotide Repeat Expansion
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human