Molecular Diagnosis of 34 Japanese Families with Leber Congenital Amaurosis Using Targeted Next Generation Sequencing.
Molecular Diagnosis of 34 Japanese Families with Leber Congenital Amaurosis Using Targeted Next Generation Sequencing.
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DOI：
10.1038/s41598-018-26524-z
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发表时间：
2018-05-29
影响因子：
4.6
通讯作者：
Hotta Y
中科院分区：
文献类型：
--
作者：
Hosono K;Nishina S;Yokoi T;Katagiri S;Saitsu H;Kurata K;Miyamichi D;Hikoya A;Mizobuchi K;Nakano T;Minoshima S;Fukami M;Kondo H;Sato M;Hayashi T;Azuma N;Hotta Y
莱伯先天性黑朦（Leber congenital amaurosis， LCA）是一种遗传和临床异质性疾病，是遗传性视网膜营养不良（IRD）最严重的形式。本研究报道了34个日本LCA家族（包括先前报道的3个家族）已知LCA和ird相关基因的突变谱和频率。通过靶向下一代测序（TS）分析了74个LCA和ird相关基因，而最近发现的LCA相关基因以及无法使用这种方法筛选的已知变异，则通过额外的Sanger测序，远程聚合酶链反应和/或拷贝数变异分析进行了评估。这些分析的结果显示，在所分析的34个家族中的19个中，有12个基因（9个lca相关基因和3个其他ird相关基因）存在30个潜在的致病变异。最常见的突变基因是CRB1、NMNAT1和RPGRIP1。研究结果还显示，在分析的日本人群中发现的突变谱和频率与之前在其他种族背景中发现的突变谱和频率明显不同。最后，本研究首次对日本大型LCA队列进行了基于ngs的分子诊断，检出率约为56%，表明TS是日本人群LCA病例分子诊断的一种有价值的方法。
Leber congenital amaurosis (LCA) is a genetically and clinically heterogeneous disease, and represents the most severe form of inherited retinal dystrophy (IRD). The present study reports the mutation spectra and frequency of known LCA and IRD-associated genes in 34 Japanese families with LCA (including three families that were previously reported). A total of 74 LCA- and IRD-associated genes were analysed via targeted-next generation sequencing (TS), while recently discovered LCA-associated genes, as well as known variants not able to be screened using this approach, were evaluated via additional Sanger sequencing, long-range polymerase chain reaction, and/or copy number variation analyses. The results of these analyses revealed 30 potential pathogenic variants in 12 (nine LCA-associated and three other IRD-associated) genes among 19 of the 34 analysed families. The most frequently mutated genes were CRB1, NMNAT1, and RPGRIP1. The results also showed the mutation spectra and frequencies identified in the analysed Japanese population to be distinctly different from those previously identified for other ethnic backgrounds. Finally, the present study, which is the first to conduct a NGS-based molecular diagnosis of a large Japanese LCA cohort, achieved a detection rate of approximately 56%, indicating that TS is a valuable method for molecular diagnosis of LCA cases in the Japanese population.
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影响因子：
30.8
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.
通讯作者：
Pierce, Eric A.
影响因子：
3.7
作者：
Hosono K;Ishigami C;Takahashi M;Park DH;Hirami Y;Nakanishi H;Ueno S;Yokoi T;Hikoya A;Fujita T;Zhao Y;Nishina S;Shin JP;Kim IT;Yamamoto S;Azuma N;Terasaki H;Sato M;Kondo M;Minoshima S;Hotta Y
通讯作者：
Hotta Y
影响因子：
1.9
作者：
Hosono K;Harada Y;Kurata K;Hikoya A;Sato M;Minoshima S;Hotta Y
通讯作者：
Hotta Y
影响因子：
3.9
作者：
Neveling, Kornelia;Collin, Rob W. J.;Gilissen, Christian;van Huet, Ramon A. C.;Visser, Linda;Kwint, Michael P.;Gijsen, Sabine J.;Zonneveld, Marijke N.;Wieskamp, Nienke;de Ligt, Joep;Siemiatkowska, Anna M.;Hoefsloot, Lies H.;Buckley, Michael F.;Kellner, Ulrich;Branham, Kari E.;den Hollander, Anneke I.;Hoischen, Alexander;Hoyng, Carel;Klevering, B. Jeroen;van den Born, L. Ingeborgh;Veltman, Joris A.;Cremers, Frans P. M.;Scheffer, Hans
通讯作者：
Scheffer, Hans
影响因子：
9.8
作者：
Davidson, Alice E.;Millar, Ian D.;Manson, Forbes D. C.
通讯作者：
Manson, Forbes D. C.