title: A novel missense NMNAT1 mutation identified in a consanguineous family with Leber congenital amaurosis by targeted next generation sequencing.
abstract: Leber congenital amaurosis is the earliest onset and most severe inherited retinal dystrophy. Mutations in 21 genes have been identified to be responsible for LCA. To detect the causative variants, we performed targeted next generation sequencing in two affected siblings of a consanguineous Chinese family with suspected LCA. A novel homozygous missense mutation (c.721C>T, p. Pro241Ser) of NMNAT1 has been identified. The mutation was inherited from their consanguineous parents who were heterozygous and was absent in 300 unrelated healthy individuals. NMNAT1, which encodes the nicotinamide mononucleotide adenylyltransferase 1, has been recently identified to be one of the LCA-causing genes. Our results expanded the spectrum of mutations in NMNAT1. In this study, targeted next generation sequencing provides an accurate and efficient method for identifying mutations in hereditary diseases with highly genetic and clinical heterogeneity.
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China; Laboratory of Molecular Epidemiology for Birth Defect, West China Institute of Women and Children's Health, Sichuan University, Chengdu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China; Laboratory of Molecular Epidemiology for Birth Defect, West China Institute of Women and Children's Health, Sichuan University, Chengdu, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China; Laboratory of Molecular Epidemiology for Birth Defect, West China Institute of Women and Children's Health, Sichuan University, Chengdu, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China; School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Li
authors.affiliation: Xiangxi Maternal and Child Health Hospital, Jishou, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pediatric, West China Second University Hospital, Sichuan University, Chengdu, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Su
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yi
authors.affiliation: National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu, China; Laboratory of Molecular Epidemiology for Birth Defect, West China Institute of Women and Children's Health, Sichuan University, Chengdu, China. Electronic address: zhujun028@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000328:Adult; D002648:Child; D003241:Consanguinity; D005260:Female; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D057130:Leber Congenital Amaurosis; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics*; D010375:Pedigree
chemical_list: C484007:NMNAT1 protein, human; D009612:Nicotinamide-Nucleotide Adenylyltransferase
keywords: LCA; Nicotinamide nucleotide adenylyltransferase 1 gene; Variant