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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Age of Onset
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Child
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Child, Preschool
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Cohort Studies
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Genetic Predisposition to Disease
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Humans
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Leber Congenital Amaurosis / complications
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Leber Congenital Amaurosis / epidemiology
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Leber Congenital Amaurosis / genetics*
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Macular Degeneration / complications
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Macular Degeneration / epidemiology
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Macular Degeneration / genetics*
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Mutation* / physiology
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Nicotinamide-Nucleotide Adenylyltransferase / genetics*
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Optic Atrophy / complications
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Optic Atrophy / epidemiology
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Optic Atrophy / genetics*
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Polymorphism, Single Nucleotide / physiology
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Severity of Illness Index
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Young Adult
Substances
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NMNAT1 protein, human
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Nicotinamide-Nucleotide Adenylyltransferase