title: Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy.
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.
authors: Department of Genetics, Institut National de la Santé et de la Recherche Médicale U, Université Paris Descartes-Sorbonne Paris Cité, France.
authors: Isabelle
authors: I
authors: Perrault
authors: Sylvain
authors: S
authors: Hanein
authors: Xavier
authors: X
authors: Zanlonghi
authors: Valérie
authors: V
authors: Serre
authors: Michael
authors: M
authors: Nicouleau
authors: Sabine
authors: S
authors: Defoort-Delhemmes
authors: Nathalie
authors: N
authors: Delphin
authors: Lucas
authors: L
authors: Fares-Taie
authors: Sylvie
authors: S
authors: Gerber
authors: Olivia
authors: O
authors: Xerri
authors: Catherine
authors: C
authors: Edelson
authors: Alice
authors: A
authors: Goldenberg
authors: Alice
authors: A
authors: Duncombe
authors: Gylène
authors: G
authors: Le Meur
authors: Christian
authors: C
authors: Hamel
authors: Eduardo
authors: E
authors: Silva
authors: Patrick
authors: P
authors: Nitschke
authors: Patrick
authors: P
authors: Calvas
authors: Arnold
authors: A
authors: Munnich
authors: Olivier
authors: O
authors: Roche
authors: Hélène
authors: H
authors: Dollfus
authors: Josseline
authors: J
authors: Kaplan
authors: Jean-Michel
authors: JM
authors: Rozet
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D008268:Macular Degeneration / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation / Q000502:physiology; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics*; D009896:Optic Atrophy / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C484007:NMNAT1 protein, human; D009612:Nicotinamide-Nucleotide Adenylyltransferase