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

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.Foundation Fighting Blindness (FFB)985 Project Grant from the Ministry of Education of ChinaQiangjiang Research Talent grantScience and Technology Department of Zhejiang ProvinceNatural Science Foundation of Zhejiang ProvinceOregon Health & Science UniversityBeijing Genom Inst BGI Shenzhen, Shenzhen, Peoples R ChinaCasey Eye Inst, Mol Diagnost Lab, Portland, OR USAZhejiang Univ, Struct Biol Ctr, Inst Life Sci, Hangzhou 310003, Zhejiang, Peoples R ChinaZhejiang Univ, Sch Med, Affiliated Hosp 1, Ctr Genet & Genom Med, Hangzhou 310003, Zhejiang, Peoples R ChinaWomens & Childrens Hosp, SA Clin Genet Serv, Adelaide, SA, AustraliaRetina Fdn SW, Dallas, TX USASickKids Hosp, Dept Ophthalmol, Toronto, ON, CanadaOregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USAUniv Fed Goias, Ctr Referencia Oftalmol CEROF, Dept Ocular Genet, Goiania, Go, BrazilUniv Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilQiangjiang Research Talent grant: 2006R10018Natural Science Foundation of Zhejiang Province: R2100439Oregon Health & Science University: IRB00008083Web of Scienc