Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort

被引：43

作者：

Nakamura, Ryoichi ^{[1
]}

Sone, Jun ^{[1
]}

Atsuta, Naoki ^{[1
]}

Tohnai, Genki ^{[1
]}

Watanabe, Hazuki ^{[1
,2
]}

Yokoi, Daichi ^{[1
]}

Nakatochi, Masahiro ^{[3
]}

Watanabe, Hirohisa ^{[1
,4
]}

Ito, Mizuki ^{[1
]}

Senda, Jo ^{[1
,5
]}

Katsuno, Masahisa ^{[1
]}

Tanaka, Fumiaki ^{[6
]}

Li, Yuanzhe ^{[7
]}

Izumi, Yuishin ^{[8
]}

Morita, Mitsuya ^{[9
]}

Taniguchi, Akira ^{[10
]}

Kano, Osamu ^{[11
]}

Oda, Masaya ^{[12
]}

Kuwabara, Satoshi ^{[13
]}

Abe, Koji ^{[14
]}

Aiba, Ikuko ^{[15
]}

Okamoto, Koichi ^{[16
]}

Mizoguchi, Kouichi ^{[17
]}

Hasegawa, Kazuko ^{[18
]}

Aoki, Masashi ^{[19
]}

Hattori, Nobutaka ^{[7
]}

Tsuji, Shoji ^{[20
]}

Nakashima, Kenji ^{[21
]}

Kaji, Ryuji

Sobue, Gen ^{[1
,22
]}

机构：

[1] Nagoya Univ, Grad Sch Med, Dept Neurol, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan

[2] Japanese Red Cross Nagoya Daiichi Hosp, Dept Neurol, Nagoya, Aichi, Japan

[3] Nagoya Univ Hosp, Ctr Adv Med & Clin Res, Bioinformat Sect, Nagoya, Aichi, Japan

[4] Nagoya Univ, Brain & Mind Res Ctr, Nagoya, Aichi 4648601, Japan

[5] Komaki City Hosp, Dept Neurol, Komaki, Japan

[6] Yokohama City Univ, Grad Sch Med, Dept Neurol & Stroke Med, Yokohama, Kanagawa 232, Japan

[7] Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan

[8] Univ Tokushima, Grad Sch, Inst Biomed Sci, Dept Neurol, Tokushima, Japan

[9] Jichi Med Univ, Dept Internal Med, Div Neurol, Tochigi, Japan

[10] Mie Univ, Grad Sch Med, Dept Neurol, Tsu, Mie 514, Japan

[11] Toho Univ, Sch Med, Dept Internal Med, Div Neurol, Tokyo, Japan

[12] Vihara Hananosato Hosp, Dept Neurol, Miyoshi, Japan

[13] Chiba Univ, Grad Sch Med, Dept Neurol, 1-8-1 Inohana, Chiba, Japan

[14] Okayama Univ, Grad Sch Med, Dept Neurol, Okayama, Japan

[15] Natl Hosp Org Higashinagoya Natl Hosp, Dept Neurol, Nagoya, Aichi, Japan

[16] Geriatr Res Inst & Hosp, Dept Neurol, Maebashi, Gunma, Japan

[17] Natl Hosp Org Shizuoka Fuji Hosp, Dept Neurol, Fujinomiya, Japan

[18] Sagamihara Natl Hosp, Natl Hosp Org, Div Neurol, Sagamihara, Kanagawa, Japan

[19] Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 980, Japan

[20] Univ Tokyo, Grad Sch Sci, Dept Neurol, Tokyo 113, Japan

[21] Tottori Univ, Fac Med, Dept Brain & Neurosci, Div Neurol, Yonago, Tottori, Japan

[22] Nagoya Univ, Grad Sch Med, Res Div Dementia & Neurodegenerat Dis, Nagoya, Aichi 4648601, Japan

来源：

NEUROBIOLOGY OF AGING | 2016年 / 39卷

关键词：

Amyotrophic lateral sclerosis; Japan; Genetic screening; Next-generation sequencer; AMYOTROPHIC-LATERAL-SCLEROSIS; HEXANUCLEOTIDE REPEAT EXPANSION; FAMILIAL ALS; MUTATIONS; FUS; C9ORF72; ANTICIPATION; PENETRANCE; GENETICS; JUVENILE;

D O I：

10.1016/j.neurobiolaging.2015.11.030

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

We investigated the frequency and contribution of variants of the 28 known amyotrophic lateral sclerosis (ALS)-related genes in Japanese ALS patients. We designed a multiplex, polymerase chain reaction-based primer panel to amplify the coding regions of the 28 ALS-related genes and sequenced DNA samples from 257 Japanese ALS patients using an Ion Torrent PGM sequencer. We also performed exome sequencing and identified variants of the 28 genes in an additional 251 ALS patients using an Illumina HiSeq 2000 platform. We identified the known ALS pathogenic variants and predicted the functional properties of novel nonsynonymous variants in silico. These variants were confirmed by Sanger sequencing. Known pathogenic variants were identified in 19 (48.7%) of the 39 familial ALS patients and 14 (3.0%) of the 469 sporadic ALS patients. Thirty-two sporadic ALS patients (6.8%) harbored 1 or 2 novel nonsynonymous variants of ALS-related genes that might be deleterious. This study reports the first extensive genetic screening of Japanese ALS patients. These findings are useful for developing genetic screening and counseling strategies for such patients. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：219.e1 / 219.e8

页数：8

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