疾病特异性变异解读强调了 2325 名日本视网膜色素变性及相关疾病患者的遗传发现。

IF 3.5 2区 医学 Q2 GENETICS & HEREDITY Journal of Medical Genetics Pub Date : 2024-06-20 DOI:10.1136/jmg-2023-109750
Kensuke Goto, Yoshito Koyanagi, Masato Akiyama, Yusuke Murakami, Masatoshi Fukushima, Kohta Fujiwara, Hanae Iijima, Mitsuyo Yamaguchi, Mikiko Endo, Kazuki Hashimoto, Masataka Ishizu, Toshiaki Hirakata, Kei Mizobuchi, Masakazu Takayama, Junya Ota, Ai Fujita Sajiki, Taro Kominami, Hiroaki Ushida, Kosuke Fujita, Hiroki Kaneko, Shinji Ueno, Takaaki Hayashi, Chikashi Terao, Yoshihiro Hotta, Akira Murakami, Kazuki Kuniyoshi, Shunji Kusaka, Yuko Wada, Toshiaki Abe, Toru Nakazawa, Yasuhiro Ikeda, Yukihide Momozawa, Koh-Hei Sonoda, Koji M Nishiguchi
{"title":"疾病特异性变异解读强调了 2325 名日本视网膜色素变性及相关疾病患者的遗传发现。","authors":"Kensuke Goto, Yoshito Koyanagi, Masato Akiyama, Yusuke Murakami, Masatoshi Fukushima, Kohta Fujiwara, Hanae Iijima, Mitsuyo Yamaguchi, Mikiko Endo, Kazuki Hashimoto, Masataka Ishizu, Toshiaki Hirakata, Kei Mizobuchi, Masakazu Takayama, Junya Ota, Ai Fujita Sajiki, Taro Kominami, Hiroaki Ushida, Kosuke Fujita, Hiroki Kaneko, Shinji Ueno, Takaaki Hayashi, Chikashi Terao, Yoshihiro Hotta, Akira Murakami, Kazuki Kuniyoshi, Shunji Kusaka, Yuko Wada, Toshiaki Abe, Toru Nakazawa, Yasuhiro Ikeda, Yukihide Momozawa, Koh-Hei Sonoda, Koji M Nishiguchi","doi":"10.1136/jmg-2023-109750","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases.</p><p><strong>Methods: </strong>We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines.</p><p><strong>Results: </strong>A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with <i>EYS</i> accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases.</p><p><strong>Conclusion: </strong>A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases.\",\"authors\":\"Kensuke Goto, Yoshito Koyanagi, Masato Akiyama, Yusuke Murakami, Masatoshi Fukushima, Kohta Fujiwara, Hanae Iijima, Mitsuyo Yamaguchi, Mikiko Endo, Kazuki Hashimoto, Masataka Ishizu, Toshiaki Hirakata, Kei Mizobuchi, Masakazu Takayama, Junya Ota, Ai Fujita Sajiki, Taro Kominami, Hiroaki Ushida, Kosuke Fujita, Hiroki Kaneko, Shinji Ueno, Takaaki Hayashi, Chikashi Terao, Yoshihiro Hotta, Akira Murakami, Kazuki Kuniyoshi, Shunji Kusaka, Yuko Wada, Toshiaki Abe, Toru Nakazawa, Yasuhiro Ikeda, Yukihide Momozawa, Koh-Hei Sonoda, Koji M Nishiguchi\",\"doi\":\"10.1136/jmg-2023-109750\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases.</p><p><strong>Methods: </strong>We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines.</p><p><strong>Results: </strong>A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with <i>EYS</i> accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases.</p><p><strong>Conclusion: </strong>A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.</p>\",\"PeriodicalId\":16237,\"journal\":{\"name\":\"Journal of Medical Genetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medical Genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jmg-2023-109750\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jmg-2023-109750","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

背景:随着遗传性视网膜营养不良症(IRD)基因特异性疗法的发展,各研究机构统一的变异解读变得越来越重要。本研究旨在根据美国医学遗传学和基因组学学院以及分子病理学协会的规则,应用日本 IRD 患者标准化变异解读指南(J-IRD-VI 指南),更新大量日本 RP 患者中 86 个视网膜色素变性(RP)相关基因的遗传结果,并评估这些基因在 RP 相关疾病中的贡献:我们评估了 2325 名患有 RP(n=2155,包括之前用相同测序面板测序的 n=1204)和相关疾病(n=170,新分析的)的探明者,包括乌谢尔综合征、Leber 先天性羊膜炎和锥体-杆状营养不良症(CRD)。对 86 个基因进行了目标测序。结果显示,共发现 3564 个变异基因:结果:共检测到 3564 个变异,其中 524 个变异被解释为致病或可能致病。在这 524 个变异中,有 280 个(53.4%)在我们之前对 1204 名 RP 患者的研究中未被检测到或被解释为意义不明的变异或良性变异。因此,RP 患者的基因诊断率为 38.6%,其中 EYS 患者占基因诊断患者的 46.7%,诊断率比我们之前的研究提高了 9%。CRD患者的基因诊断率为28.2%,RP相关基因的贡献率明显高于其他相关疾病:结论:利用 J-IRD-VI 指南进行的大规模基因分析突出了日本 IRD 患者的人群特异性基因发现;这些发现为基因特异性疗法的临床应用奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases.

Background: As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases.

Methods: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines.

Results: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases.

Conclusion: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
期刊最新文献
Heterozygous de novo variants in HSPD1 cause hypomyelinating leukodystrophy through impaired HSP60 oligomerisation. Clinical and mutational signatures of CRB1-associated retinopathies: a multicentre study. Six at Sixty. Malignant peripheral nerve sheath tumours in NF1: 20-year review of a highly cited paper. WDR45 variants as a major cause for a clinically variable intellectual disability syndrome from early infancy in females. Accurate prenatal diagnosis of facioscapulohumeral muscular dystrophy 1 using nanopore sequencing.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1