EYS is a major gene involved in retinitis pigmentosa in Japan: genetic landscapes revealed by stepwise genetic screening.
EYS is a major gene involved in retinitis pigmentosa in Japan: genetic landscapes revealed by stepwise genetic screening.
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在日本，EYS是与视网膜色素变性有关的一个主要基因：通过逐步遗传筛查揭示了遗传景观。
DOI：
10.1038/s41598-020-77558-1
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发表时间：
2020-11-27
影响因子：
4.6
通讯作者：
Tsujikawa A
中科院分区：
文献类型：
--
作者：
Numa S;Oishi A;Higasa K;Oishi M;Miyata M;Hasegawa T;Ikeda HO;Otsuka Y;Matsuda F;Tsujikawa A
下一代测序（NGS）极大地推进了遗传性疾病致病基因和变异体的研究。虽然有时确定NGS中已鉴定变体的致病性具有挑战性，但美国医学遗传学和基因组学学院制定了指导方针以帮助解释。然而，对于日本视网膜色素变性（RP）患者的遗传筛查，以前的研究都没有使用该指南。考虑到EYS是日本RP的主要致病基因，我们利用该指南对220例日本RP患者进行了逐步遗传筛查。步骤1-4按顺序包括以下内容：两个主要EYS创始突变的桑格测序; EYS所有编码区的靶向测序;全基因组测序; RP 1中Alu元件插入的桑格测序，这是最近确定的RP创始突变。在检测到的变异体中，2、19、173和1个变异体被认为是致病性的，分别有8、41、44和5例患者在第1、2、3和4步中被遗传学解决。共44.5%（98/220）的患者获得遗传学解决，其中50例（51.0%）与EYS相关，5例（5.1%）与Alu元件相关。在未解决的122例患者中，22例至少有一种可能的致病变异。
Next-generation sequencing (NGS) has greatly advanced the studies of causative genes and variants of inherited diseases. While it is sometimes challenging to determine the pathogenicity of identified variants in NGS, the American College of Medical Genetics and Genomics established the guidelines to help the interpretation. However, as to the genetic screenings for patients with retinitis pigmentosa (RP) in Japan, none of the previous studies utilized the guidelines. Considering that EYS is the major causative gene of RP in Japan, we conducted stepwise genetic screening of 220 Japanese patients with RP utilizing the guidelines. Step 1–4 comprised the following, in order: Sanger sequencing for two major EYS founder mutations; targeted sequencing of all coding regions of EYS; whole genome sequencing; Sanger sequencing for Alu element insertion in RP1, a recently determined founder mutation for RP. Among the detected variants, 2, 19, 173, and 1 variant(s) were considered pathogenic and 8, 41, 44, and 5 patients were genetically solved in step 1, 2, 3, and 4, respectively. Totally, 44.5% (98/220) of the patients were genetically solved, and 50 (51.0%) were EYS-associated and 5 (5.1%) were Alu element-associated. Among the unsolved 122 patients, 22 had at least one possible pathogenic variant.
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影响因子：
1.9
作者：
Arai Y;Maeda A;Hirami Y;Ishigami C;Kosugi S;Mandai M;Kurimoto Y;Takahashi M
通讯作者：
Takahashi M
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
细胞内氯离子通道 CLCC1 突变与常染色体隐性遗传色素性视网膜炎相关
影响因子：
4.5
作者：
Li L;Jiao X;D'Atri I;Ono F;Nelson R;Chan CC;Nakaya N;Ma Z;Ma Y;Cai X;Zhang L;Lin S;Hameed A;Chioza BA;Hardy H;Arno G;Hull S;Khan MI;Fasham J;Harlalka GV;Michaelides M;Moore AT;Coban Akdemir ZH;Jhangiani S;Lupski JR;Cremers FPM;Qamar R;Salman A;Chilton J;Self J;Ayyagari R;Kabir F;Naeem MA;Ali M;Akram J;Sieving PA;Riazuddin S;Baple EL;Riazuddin SA;Crosby AH;Hejtmancik JF
通讯作者：
Hejtmancik JF
影响因子：
3.9
作者：
Bax, Nathalie M.;Sangermano, Riccardo;Cremers, Frans P. M.
通讯作者：
Cremers, Frans P. M.
影响因子：
4.5
作者：
Kim, Min Seok;Joo, Kwangsic;Woo, Se Joon
通讯作者：
Woo, Se Joon