NMNAT1 Mutations Cause Leber Congenital Amaurosis

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NMNAT1 Mutations Cause Leber Congenital Amaurosis

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Title: NMNAT1 Mutations Cause Leber Congenital Amaurosis
Author: Falk, Marni J; Nakamaru-Ogiso, Eiko; Kannabiran, Chitra; Chakarova, Christina; Audo, Isabelle; Mackay, Donna S; Zeitz, Christina; Borman, Arundhati Dev; Shukla, Rachna; Palavalli, Lakshmi; Mohand-Said, Saddek; Waseem, Naushin H; Jalali, Subhadra; Perin, Juan C; Ostrovsky, Julian; Xiao, Rui; Bhattacharya, Shomi S; Webster, Andrew R; Sahel, José-Alain; Moore, Anthony T; Gai, Xiaowu; Zhang, Qi; Kelly, Zoe; Staniszewska, Magdalena; Place, Emily Margaret; Consugar, Mark Bryant; Berson, Eliot Lawrence; Liu, Qin; Pierce, Eric Adam

Note: Order does not necessarily reflect citation order of authors.

Citation: Falk, Marni J., Qi Zhang, Eiko Nakamaru-Ogiso, Chitra Kannabiran, Zoe Kelly, Christina Chakarova, Isabelle Audo, et al. 2012. NMNAT1 mutations cause Leber congenital amaurosis. Nature Genetics 44(9): 1040-1045.
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Abstract: Leber congenital amaurosis (LCA) is an infantile-onset form of inherited retinal degeneration characterized by severe vision loss. Two-thirds of LCA cases are caused by mutations in 17 known disease genes (RetNet Retinal Information Network). Using exome sequencing, we identified a homozygous missense mutation (c.25G>A, p.Val9Met) in NMNAT1 as likely disease-causing in two siblings of a consanguineous Pakistani kindred affected by LCA. This mutation segregated with disease in their kindred, including in three other children with LCA. NMNAT1 resides in the previously identified LCA9 locus and encodes the nuclear isoform of nicotinamide mononucleotide adenylyltransferase, a rate-limiting enzyme in nicotinamide adenine dinucleotide \((NAD^+)\) biosynthesis. Functional studies showed the p.Val9Met mutation decreased NMNAT1 enzyme activity. Sequencing NMNAT1 in 284 unrelated LCA families identified 14 rare mutations in 13 additional affected individuals. These results are the first to link an NMNAT isoform to disease and indicate that NMNAT1 mutations cause LCA.
Published Version: doi:10.1038/ng.2361
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3454532/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10622980
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