Whole-Exome Sequencing in Turkish Patients with Inherited Retinal Dystrophies Reveals Novel Variants in Ten Genes

IF 0.9 4区医学 Q4 GENETICS & HEREDITY

Molecular Syndromology Pub Date : 2023-12-28 DOI:10.1159/000535590

Muserref Basdemirci, Hatice Kocak Eker

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引用次数: 0

Abstract

Introduction: Inherited retinal dystrophies (IRDs) associated with more than 300 genes are a clinically and genetically heterogeneous group of retinal diseases. This study aimed to identify causative gene variants and molecular basis of Turkish patients with IRD. Methods: Whole-exome sequencing was performed in 28 unrelated patients. The potential pathogenicity of variants was evaluated using the American College of Medical Genetics variant interpretation guidelines, in silico prediction tools, published literature or Human Gene Mutation Database, and compatibility with inheritance patterns or known phenotypes. Results: Causative variants in 21 genes, including MERTK, SNRP200, MYO7A, AIPL1, RDH12, OTX2, ADGRV1, RPGRIP1, SPATA7, USH2A, MFSD8, CDHR1, EYS, CACNA1F, CNGA3, RDH5, TULP1, BBS2, BEST1, RS1, GUCY2D were detected in 26 (92.9%) of 28 patients. The most prevalent causative variants were observed MERTK (10.7% of cases), followed by CDHR1, AIPL1, RDH12, SPATA7, CNGA3, TULP1 (7.1% of cases, each). The most common variant type in this study was missense variants (53%), followed by frameshift (21%), nonsense (20%), and splice (6%). Twelve novel variants, 6 of frameshift and 6 of missense, were detected in ten genes. Retinitis pigmentosa was the most common phenotype followed by Leber congenital amaurosis. Conclusion: This study provides an overview of causative gene variants in Turkish patients with IRD. Variants identified in this study expand the variant spectrum of IRD genes. We believe it is essential to combine molecular and clinical data to diagnose IRD patients, especially with the emergence of therapeutic options.

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土耳其遗传性视网膜营养不良症患者的全基因组测序发现十个基因的新变异

导言：与 300 多个基因相关的遗传性视网膜营养不良症（IRD）是一组临床和遗传异质性视网膜疾病。本研究旨在确定土耳其 IRD 患者的致病基因变异和分子基础。研究方法对 28 名无亲属关系的患者进行了全外显子组测序。使用美国医学遗传学会变异解释指南、硅预测工具、已发表文献或人类基因突变数据库，以及与遗传模式或已知表型的兼容性，对变异的潜在致病性进行评估。结果：28名患者中有26人（92.9%）检测到21个基因的致病变异，包括MERTK、SNRP200、MYO7A、AIPL1、RDH12、OTX2、ADGRV1、RPGRIP1、SPATA7、USH2A、MFSD8、CDHR1、EYS、CACNA1F、CNGA3、RDH5、TULP1、BBS2、BEST1、RS1、GUCY2D。最常见的致病变异是 MERTK（占 10.7%），其次是 CDHR1、AIPL1、RDH12、SPATA7、CNGA3 和 TULP1（各占 7.1%）。本研究中最常见的变异类型是错义变异（53%），其次是移码变异（21%）、无义变异（20%）和剪接变异（6%）。在 10 个基因中发现了 12 个新变异，其中 6 个为移帧变异，6 个为错义变异。视网膜色素变性是最常见的表型，其次是先天性弱视。结论本研究概述了土耳其 IRD 患者的致病基因变异。本研究发现的变异扩大了 IRD 基因的变异谱。我们认为，结合分子数据和临床数据诊断 IRD 患者至关重要，尤其是在治疗方案不断涌现的今天。

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来源期刊

Molecular Syndromology Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

1.70

自引率

9.10%

发文量

期刊介绍： ''Molecular Syndromology'' publishes high-quality research articles, short reports and reviews on common and rare genetic syndromes, aiming to increase clinical understanding through molecular insights. Topics of particular interest are the molecular basis of genetic syndromes, genotype-phenotype correlation, natural history, strategies in disease management and novel therapeutic approaches based on molecular findings. Research on model systems is also welcome, especially when it is obviously relevant to human genetics. With high-quality reviews on current topics the journal aims to facilitate translation of research findings to a clinical setting while also stimulating further research on clinically relevant questions. The journal targets not only medical geneticists and basic biomedical researchers, but also clinicians dealing with genetic syndromes. With four Associate Editors from three continents and a broad international Editorial Board the journal welcomes submissions covering the latest research from around the world.