Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis

• Published in: Nature genetics Vol. 44; no. 9; pp. 972 - 974
• Main Authors: Chiang, Pei-Wen, Wang, Juan, Chen, Yang, Fu, Quan, Zhong, Jing, Chen, Yanhua, Yi, Xin, Wu, Renhua, Gan, Haixue, Shi, Yong, Chen, Yanling, Barnett, Christopher, Wheaton, Dianna, Day, Megan, Sutherland, Joanne, Heon, Elise, Weleber, Richard G, Gabriel, Luis Alexandre Rassi, Cong, Peikuan, Chuang, KuangHsiang, Ye, Sheng, Sallum, Juliana Maria Ferraz, Qi, Ming
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2012; Nature Publishing Group
• Subjects: 631/208/2489/144; 631/208/514/1948; 692/699; Adolescent; Adult; Age; Agriculture; Allelomorphism; Animal Genetics and Genomics; Biological and medical sciences; Biomedicine; brief-communication; Cancer Research; Child; Child, Preschool; Chromosomes; Coenzymes; Cohort Studies; DNA Mutational Analysis; Dystrophy; Exome - genetics; Exome sequencing; Experiments; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Gene mutations; Gene therapy; Genetic aspects; Genetic Predisposition to Disease; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Human Genetics; Humans; Infant; Insects; Leber Congenital Amaurosis - epidemiology; Leber Congenital Amaurosis - genetics; Leber's congenital amaurosis; Male; Medical sciences; Mutation; Mutation - physiology; Nicotinamide-Nucleotide Adenylyltransferase - genetics; Ophthalmology; Properties; Proteins; Retinopathies; Sequence Analysis, DNA; Young Adult; China; Eye disease; Leber amaurosis; Retinopathy; Congenital; Identification; Mutation; Sequencing; Genetic disease
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2370

Ming Qi and colleagues report that compound heterozygous mutations in NMNAT1 cause Leber congenital amaurosis, a childhood form of retinal dystrophy. NMNAT1 encodes an enzyme previously implicated in protection against axonal degeneration. Leber congenital amaurosis (LCA) is an autosomal recessive retinal dystrophy that manifests with genetic heterogeneity. We sequenced the exome of an individual with LCA and identified nonsense (c.507G>A, p.Trp169*) and missense (c.769G>A, p.Glu257Lys) mutations in NMNAT1 , which encodes an enzyme in the nicotinamide adenine dinucleotide (NAD) biosynthesis pathway implicated in protection against axonal degeneration. We also found NMNAT1 mutations in ten other individuals with LCA, all of whom carry the p.Glu257Lys variant.