NMNAT1 mutations cause Leber congenital amaurosis.
NMNAT1 mutations cause Leber congenital amaurosis.
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DOI：
10.1038/ng.2361
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发表时间：
2012-09
期刊：
影响因子：
30.8
通讯作者：
Pierce, Eric A.
中科院分区：
文献类型：
--
作者：
Falk, Marni J.;Zhang, Qi;Nakamaru-Ogiso, Eiko;Kannabiran, Chitra;Fonseca-Kelly, Zoe;Chakarova, Christina;Audo, Isabelle;Mackay, Donna S.;Zeitz, Christina;Borman, Arundhati Dev;Staniszewska, Magdalena;Shukla, Rachna;Palavalli, Lakshmi;Mohand-Said, Saddek;Waseem, Naushin H.;Jalali, Subhadra;Perin, Juan C.;Place, Emily;Ostrovsky, Julian;Xiao, Rui;Bhattacharya, Shomi S.;Consugar, Mark;Webster, Andrew R.;Sahel, Jose-Alain;Moore, Anthony T.;Berson, Eliot L.;Liu, Qin;Gai, Xiaowu;Pierce, Eric A.
Leber先天性黑色素(LCA)是一种以严重视力丧失为特征的遗传性视网膜变性的婴儿期发病形式。三分之二的LCA病例是由17个已知疾病基因的突变引起的(RetNet视网膜信息网)。利用外显子组测序，我们发现NMNA1中的一个纯合子错义突变(C.25G>；A，p.Val9Met)可能是一个受LCA影响的巴基斯坦血亲的兄弟姐妹的致病因素。这种突变与他们家族中的疾病分离，包括在其他三名患有LCA的儿童中。NMNA1位于LCA9基因座，编码烟酰胺腺嘌呤二核苷酸(NAD+)生物合成中的限速酶烟酰胺单核苷酸腺基转移酶的核异构体。功能研究表明，p.Val9Met突变降低了NMNA1酶的活性。对284个无关的LCA家系进行NMNA1测序，在另外13个受影响的个体中发现了14个罕见突变。这些结果首次将NMNAT亚型与疾病联系起来，并表明NMNA1突变导致LCA。
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.
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影响因子：
--
作者：
Jacobson, Samuel G.;Cideciyan, Artur V.;Ratnakaram, Ramakrishna;Heon, Elise;Schwartz, Sharon B.;Roman, Alejandro J.;Peden, Marc C.;Aleman, Tomas S.;Boye, Sanford L.;Sumaroka, Alexander;Conlon, Thomas J.;Calcedo, Roberto;Pang, Ji-Jing;Erger, Kirsten E.;Olivares, Melani B.;Mullins, Cristina L.;Swider, Malgorzata;Kaushal, Shalesh;Feuer, William J.;Iannaccone, Alessandro;Fishman, Gerald A.;Stone, Edwin M.;Byrne, Barry J.;Hauswirth, William W.
通讯作者：
Hauswirth, William W.
影响因子：
5.3
作者：
Liu, Q;Zuo, J;Pierce, EA
通讯作者：
Pierce, EA
DOI：
10.1083/jcb.200808042
发表时间：
2009-02-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Avery MA;Sheehan AE;Kerr KS;Wang J;Freeman MR
通讯作者：
Freeman MR
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.4
作者：
Conforti, Laura;Janeckova, Lucie;Coleman, Michael
通讯作者：
Coleman, Michael