Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy

Nat Genet. 2012 Sep;44(9):975-7. doi: 10.1038/ng.2357. Epub 2012 Jul 29.


In addition to its activity in nicotinamide adenine dinucleotide (NAD(+)) synthesis, the nuclear nicotinamide mononucleotide adenyltransferase NMNAT1 acts as a chaperone that protects against neuronal activity-induced degeneration. Here we report that compound heterozygous and homozygous NMNAT1 mutations cause severe neonatal neurodegeneration of the central retina and early-onset optic atrophy in 22 unrelated individuals. Their clinical presentation is consistent with Leber congenital amaurosis and suggests that the mutations affect neuroprotection of photoreceptor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child, Preschool
  • Cohort Studies
  • Genetic Predisposition to Disease
  • Humans
  • Leber Congenital Amaurosis / complications
  • Leber Congenital Amaurosis / epidemiology
  • Leber Congenital Amaurosis / genetics*
  • Macular Degeneration / complications
  • Macular Degeneration / epidemiology
  • Macular Degeneration / genetics*
  • Mutation* / physiology
  • Nicotinamide-Nucleotide Adenylyltransferase / genetics*
  • Optic Atrophy / complications
  • Optic Atrophy / epidemiology
  • Optic Atrophy / genetics*
  • Polymorphism, Single Nucleotide / physiology
  • Severity of Illness Index
  • Young Adult


  • NMNAT1 protein, human
  • Nicotinamide-Nucleotide Adenylyltransferase