Journal Article

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

Hanein, Sylvain, Defoort-Delhemmes, Sabine, Kaplan, Josseline, Goldenberg, Alice, Calvas, Patrick, Rozet, Jean-Michel, Le Meur, Gylène, Nicouleau, Michael, Hamel, Christian, Silva, Eduardo, Gerber, Sylvie, Serre, Valérie, Delphin, Nathalie, Duncombe, Alice, Edelson, Catherine, Nitschke, Patrick, Zanlonghi, Xavier, Xerri, Olivia, Dollfus, Hélène, Fares-Taie, Lucas, Munnich, Arnold, Roche, Olivier, Perrault, Isabelle

2012

Overview

Josseline Kaplan, Jean-Michel Rozet and colleagues show that biallelic mutations in NMNAT1 cause an autosomal recessive form of Leber congenital amaurosis characterized by early-onset severe macular atrophy and optic atrophy. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/2489/144 / 692/699/375/365 / Adolescent / Adult / Age of Onset / Agriculture / Animal Genetics and Genomics / Biological and medical sciences / Biomedicine / brief-communication / Cancer Research / Child / Child, Preschool / Cohort Studies / Development and progression / Disease / Diseases of visual field, optic nerve, optic chiasma and optic tracts / Fundamental and applied biological sciences. Psychology / Gene Function / Gene mutations / Genealogy / Genes / Genetic aspects / Genetic Predisposition to Disease / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Genomes / Health aspects / Human Genetics / Humans / Insects / Leber Congenital Amaurosis - complications / Leber Congenital Amaurosis - epidemiology / Leber Congenital Amaurosis - genetics / Leber's congenital amaurosis / Life Sciences / Macular degeneration / Macular Degeneration - complications / Macular Degeneration - epidemiology / Macular Degeneration - genetics / Medical sciences / Mutation / Mutation - physiology / Nicotinamide-Nucleotide Adenylyltransferase - genetics / Ophthalmology / Optic atrophy / Optic Atrophy - complications / Optic Atrophy - epidemiology / Optic Atrophy - genetics / Patient outcomes / Polymorphism, Single Nucleotide - physiology / Proteins / Retina / Retinopathies / Risk factors / Severity of Illness Index / Young Adult