Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis

Nat Genet. 2012 Sep;44(9):972-4. doi: 10.1038/ng.2370. Epub 2012 Jul 29.

Abstract

Leber congenital amaurosis (LCA) is an autosomal recessive retinal dystrophy that manifests with genetic heterogeneity. We sequenced the exome of an individual with LCA and identified nonsense (c.507G>A, p.Trp169*) and missense (c.769G>A, p.Glu257Lys) mutations in NMNAT1, which encodes an enzyme in the nicotinamide adenine dinucleotide (NAD) biosynthesis pathway implicated in protection against axonal degeneration. We also found NMNAT1 mutations in ten other individuals with LCA, all of whom carry the p.Glu257Lys variant.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • Exome / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Leber Congenital Amaurosis / epidemiology
  • Leber Congenital Amaurosis / genetics*
  • Male
  • Mutation* / physiology
  • Nicotinamide-Nucleotide Adenylyltransferase / genetics*
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • NMNAT1 protein, human
  • Nicotinamide-Nucleotide Adenylyltransferase