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

Pei-Wen Chiang; Juan Wang; Yang Chen; Quan Fu; Jing Zhong; Yanhua Chen; Xin Yi; Renhua Wu; Haixue Gan; Yong Shi; Yanling Chen; Christopher Barnett; Dianna Wheaton; Megan Day; Joanne Sutherland; Elise Heon; Richard G. Weleber; Luis Alexandre Rassi Gabriel; Peikuan Cong; Kuanghsiang Chuang; Sheng Ye; Juliana Maria Ferraz Sallum; Ming Qi

doi:10.1038/ng.2370

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

Pei-Wen Chiang, Juan Wang, Yang Chen, Quan Fu, Jing Zhong, Yanhua Chen, Xin Yi, Renhua Wu, Haixue Gan, Yong Shi, Yanling Chen, Christopher Barnett, Dianna Wheaton, Megan Day, Joanne Sutherland, Elise Heon, Richard G. Weleber, Luis Alexandre Rassi Gabriel, Peikuan Cong, Kuanghsiang ChuangSheng Ye, Juliana Maria Ferraz Sallum, Ming Qi

Ophthalmology

Research output: Contribution to journal › Article › peer-review

102 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	972-974
Number of pages	3
Journal	Nature genetics
Volume	44
Issue number	9
DOIs	https://doi.org/10.1038/ng.2370
State	Published - Sep 2012

ASJC Scopus subject areas

Genetics

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Chiang, P-W., Wang, J., Chen, Y., Fu, Q., Zhong, J., Chen, Y., Yi, X., Wu, R., Gan, H., Shi, Y., Chen, Y., Barnett, C., Wheaton, D., Day, M., Sutherland, J., Heon, E., Weleber, R. G., Gabriel, L. A. R., Cong, P., ... Qi, M. (2012). Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. Nature genetics, 44(9), 972-974. https://doi.org/10.1038/ng.2370

Chiang, P-W, Wang, J, Chen, Y, Fu, Q, Zhong, J, Chen, Y, Yi, X, Wu, R, Gan, H, Shi, Y, Chen, Y, Barnett, C, Wheaton, D, Day, M, Sutherland, J, Heon, E, Weleber, RG, Gabriel, LAR, Cong, P, Chuang, K, Ye, S, Sallum, JMF & Qi, M 2012, 'Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis', Nature genetics, vol. 44, no. 9, pp. 972-974. https://doi.org/10.1038/ng.2370

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title = "Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis",

abstract = "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.",

author = "Pei-Wen Chiang and Juan Wang and Yang Chen and Quan Fu and Jing Zhong and Yanhua Chen and Xin Yi and Renhua Wu and Haixue Gan and Yong Shi and Yanling Chen and Christopher Barnett and Dianna Wheaton and Megan Day and Joanne Sutherland and Elise Heon and Weleber, {Richard G.} and Gabriel, {Luis Alexandre Rassi} and Peikuan Cong and Kuanghsiang Chuang and Sheng Ye and Sallum, {Juliana Maria Ferraz} and Ming Qi",

note = "Funding Information: We thank the subjects and their parents for participation in this study. The primary appointment of M.Q. is at the Zhejiang University School of Medicine. P.-W.C. and R.G.W. are grateful for the support of the Foundation Fighting Blindness (FFB). P.-W.C. is especially thankful to the parents of subject 1. Without their persistence and commitment, this work would not have been possible. This project was partially supported by a 985 Project Grant from the Ministry of Education of China (to M.Q.) and by the Qiangjiang Research Talent grant (2006R10018, to M.Q.) from the Science and Technology Department of Zhejiang Province. Q.F. and S.Y. are supported by funds from the Natural Science Foundation of Zhejiang Province (R2100439). Informed consent was obtained through the Casey Eye Institute Molecular Diagnostic Laboratory for the purpose of clinical testing and, subsequently, research testing if no mutations could be identified. This study was approved by the Oregon Health & Science University research integrity office (IRB00008083).",

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AU - Chiang, Pei-Wen

AU - Wang, Juan

AU - Chen, Yang

AU - Fu, Quan

AU - Zhong, Jing

AU - Chen, Yanhua

AU - Yi, Xin

AU - Wu, Renhua

AU - Gan, Haixue

AU - Shi, Yong

AU - Chen, Yanling

AU - Barnett, Christopher

AU - Wheaton, Dianna

AU - Day, Megan

AU - Sutherland, Joanne

AU - Heon, Elise

AU - Weleber, Richard G.

AU - Gabriel, Luis Alexandre Rassi

AU - Cong, Peikuan

AU - Chuang, Kuanghsiang

AU - Ye, Sheng

AU - Sallum, Juliana Maria Ferraz

AU - Qi, Ming

N1 - Funding Information: We thank the subjects and their parents for participation in this study. The primary appointment of M.Q. is at the Zhejiang University School of Medicine. P.-W.C. and R.G.W. are grateful for the support of the Foundation Fighting Blindness (FFB). P.-W.C. is especially thankful to the parents of subject 1. Without their persistence and commitment, this work would not have been possible. This project was partially supported by a 985 Project Grant from the Ministry of Education of China (to M.Q.) and by the Qiangjiang Research Talent grant (2006R10018, to M.Q.) from the Science and Technology Department of Zhejiang Province. Q.F. and S.Y. are supported by funds from the Natural Science Foundation of Zhejiang Province (R2100439). Informed consent was obtained through the Casey Eye Institute Molecular Diagnostic Laboratory for the purpose of clinical testing and, subsequently, research testing if no mutations could be identified. This study was approved by the Oregon Health & Science University research integrity office (IRB00008083).

PY - 2012/9

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N2 - 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.

AB - 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.

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

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