Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy.
Perrault I,Hanein S,Zanlonghi X,Serre V,Nicouleau M,Defoort-Delhemmes S,Delphin N,Fares-Taie L,Gerber S,Xerri O,Edelson C,Goldenberg A,Duncombe A,Le Meur G,Hamel C,Silva E,Nitschke P,Calvas P,Munnich A,Roche O,Dollfus H,Kaplan J,Rozet J
Source :
Nat Genet
2012 Jul 29
Pmid / DOI:
22842229
Abstract
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.