C19orf44的双等位基因功能丧失变异导致视网膜变性。

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Hafiz Muhammad Jafar Hussain, Wang Meng, Yumei Li, Sabika Firasat, Mark E Pennesi, Michael B Gorin, Bin Guan, Rebecca Lynn Clark, Emma Fale-Olsen, Ranya Al Rawi, Aime Agather, Laryssa A Huryn, Paul Yang, Anna Matynia, Rui Chen
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引用次数: 0

摘要

背景:遗传性视网膜疾病(IRDs)是一类常导致进行性视力丧失,最终导致失明的疾病。其很大一部分遗传原因仍未得到解决,部分原因是未发现与疾病相关的基因或变异。这项研究旨在确定与IRDs的新的遗传联系。方法:所有患者接受全面的眼科检查,包括视网膜成像(眼底自身荧光和黄斑光学相干断层扫描)和视网膜电图检查。对临床未解决的IRD患者进行全外显子组测序和全基因组测序,并使用内部管道分析数据以确定因果变异。随后,进行Sanger测序以确认已识别的变异。结果:来自欧洲、中东和东亚的三名无关患者被鉴定出独特的晚发性视网膜变性(stargardt样表型),与C19orf44 (HGNC: 26141)的双等位基因功能丧失(LoF)变异相关,C19orf44是一种功能未知的基因。纯合变异体NM_032207.2:c.549_550del;在2例无血缘关系的患者(欧洲和中东)中鉴定出Ser185Profs*2。此外,东亚患者可能存在复合杂合LoF变异(NM_032207.2:c.1168C>T;p.Gln390*/c.976_977del;p.Leu326Lysfs*15)。结论:我们的研究结果确立了C19orf44作为具有stargardt样表型的IRD的一个新的致病基因,扩大了视网膜变性的遗传格局。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biallelic loss-of-function variants in C19orf44 lead to retinal degeneration.

Background: Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs.

Methods: All patients underwent comprehensive ophthalmological evaluation, including retinal imaging (fundus autofluorescence and macular optical coherence tomography) and electroretinogram testing. Whole exome sequencing and whole genome sequencing were performed on patients with clinically unsolved IRD, and data were analysed using an in-house pipeline to identify causal variants. Subsequently, Sanger sequencing was performed to confirm identified variants.

Results: Three unrelated patients from Europe, Middle East and East Asia were identified with unique late-onset retinal degeneration (Stargardt-like phenotype) associated with biallelic loss-of-function (LoF) variants in C19orf44 (HGNC: 26141), a gene of unknown function. The homozygous variant NM_032207.2:c.549_550del;p.Ser185Profs*2 was identified in two unrelated patients (European and Middle Eastern). Moreover, an East Asian patient had likely compound heterozygous LoF variants (NM_032207.2:c.1168C>T;p.Gln390*/c.976_977del;p.Leu326Lysfs*15).

Conclusions: Our findings establish C19orf44 as a novel disease-causing gene for IRD with Stargardt-like phenotype, expanding the genetic landscape of retinal degeneration.

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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.
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