Genetic characterization of 1210 Japanese pedigrees with inherited retinal diseases by whole-exome sequencing

IF 3.3 2区医学 Q2 GENETICS & HEREDITY Human Mutation Pub Date : 2022-10-25 DOI:10.1002/humu.24492

Akiko Suga, Kazutoshi Yoshitake, Naoko Minematsu, Kazushige Tsunoda, Kaoru Fujinami, Yozo Miyake, Kazuki Kuniyoshi, Takaaki Hayashi, Kei Mizobuchi, Shinji Ueno, Hiroko Terasaki, Taro Kominami, Nobuhisa Nao-I, Go Mawatari, Atsushi Mizota, Kei Shinoda, Mineo Kondo, Kumiko Kato, Tetsuju Sekiryu, Makoto Nakamura, Sentaro Kusuhara, Hiroyuki Yamamoto, Shuji Yamamoto, Kiyofumi Mochizuki, Hiroyuki Kondo, Itsuka Matsushita, Shuhei Kameya, Takeo Fukuchi, Tetsuhisa Hatase, Masayuki Horiguchi, Yoshiaki Shimada, Atsuhiro Tanikawa, Shuichi Yamamoto, Gen Miura, Nana Ito, Akira Murakami, Takuro Fujimaki, Yoshihiro Hotta, Koji Tanaka, Takeshi Iwata

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引用次数: 8

Abstract

Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.

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用全外显子组测序分析1210个日本遗传性视网膜疾病家系的遗传特征

遗传性视网膜疾病(IRDs)包括一组表型和遗传异质性的眼部疾病，通过进行性视网膜变性导致视力丧失。在这里，我们报告了通过日本眼遗传联盟登记的1210个IRD谱系的遗传特征，并通过全外显子组测序进行了分析。最常见的表型是视网膜色素变性(RP, 43%)，其次是黄斑营养不良/锥体或锥杆营养不良(MD/CORD, 13%)。总共在37%(448/1210)的家系中鉴定出67个致病基因。第一和第二常见的突变基因是EYS和RP1，主要与常染色体隐性(ar) RP、RP和arMD/CORD相关。对总变异频率和表型的检测显示，一个频繁的EYS错义变异具有很高的可信度(c.2528G> a)。除了arRP的两个已知的EYS始创突变(c.4957dupA和c.8805C>G)外，我们还在arMD/CORD患者中发现了一个常见的RP1变异(c.5797C>T)。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Mutation 医学-遗传学

CiteScore

8.40

自引率

5.10%

发文量

190

审稿时长

2 months

期刊介绍： Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.