Deciphering the genetic basis of inherited retinal dystrophies via whole-exome sequencing in a Turkish cohort.

IF 1.8 3区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Vision Pub Date : 2025-12-12 eCollection Date: 2025-01-01

Zulal Keles, Ozlem Ural Fatihoglu, Ziya Ayhan, Ali O Saatci, Ahmet O Caglayan, Ayfer Ulgenalp

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引用次数: 0

Abstract

Purpose: Inherited retinal dystrophies (IRDs) encompass a genetically and clinically heterogeneous group of disorders, with over 300 genes currently implicated. Early and precise genetic diagnosis is critical for advancing targeted gene therapies and personalized treatment strategies. This study aims to investigate genetic findings in IRDs using whole-exome sequencing (WES) in a cohort of affected individuals.

Methods: WES was performed on 34 unrelated probands diagnosed with diverse IRD subtypes. Variant analysis focused on identifying clinically relevant variants consistent with the patients' phenotypes and inheritance patterns, emphasizing novel and rare variants.

Results: Clinically relevant variants consistent with the patients' phenotypes and inheritance patterns were identified in 24 cases. Among these, four variants were novel: RP2 c.181_182del, CYP4V2 c.377T>G, RPGR c.1414G>A, and RPE65 c.267C>G. Additionally, we identified a patient with isolated IRD carrying a homozygous IFT81 c.1969C>T (p.Gln657Ter) variant, a gene typically associated with syndromic phenotypes. Furthermore, we reported a relatively rare presentation of ARSG-related Usher syndrome in a patient harboring a homozygous ARSG c.263G>T (p.Arg88Leu) alteration.

Conclusions: This study underscores the diagnostic power of WES in IRDs, revealing novel variants and supporting its integration into clinical practice to enhance early diagnosis and enable precision medicine.

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在土耳其队列中通过全外显子组测序破译遗传性视网膜营养不良的遗传基础。

目的：遗传性视网膜营养不良症（IRDs）包括一组遗传和临床异质性的疾病，目前涉及300多个基因。早期和精确的基因诊断对于推进靶向基因治疗和个性化治疗策略至关重要。本研究旨在利用全外显子组测序（WES）在受影响个体队列中研究IRDs的遗传发现。方法：对34例诊断为不同IRD亚型的无血缘关系先证者进行WES检测。变异分析侧重于识别与患者表型和遗传模式一致的临床相关变异，强调新颖和罕见的变异。结果：在24例患者中发现了与患者表型和遗传模式一致的临床相关变异。其中，4个变异是新发现的：RP2 c.181_182del、CYP4V2 c.377T b> G、rpegr c.1414G>A和RPE65 c.267C>G。此外，我们发现了一名分离的IRD患者携带纯合子IFT81 c.1969C>T （p.Gln657Ter）变异，该基因通常与综合征表型相关。此外，我们报道了一例相对罕见的ARSG相关Usher综合征，患者携带纯合子ARSG c.263G>T （p.a g88leu）改变。结论：本研究强调了WES在ird中的诊断能力，揭示了新的变异，并支持将其整合到临床实践中，以加强早期诊断和实现精准医疗。

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

Molecular Vision 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.