全外显子组测序揭示遗传性视网膜疾病患者的分子诊断
Revealing Molecular Diagnosis With Whole Exome Sequencing in Patients With Inherited Retinal Disorders.
作者信息
Yavas Cuneyd, Arvas Yunus Emre, Dogan Mustafa, Gezdirici Alper, Aslan Elif Sibel, Karapapak Murat, Barıs Savas, Eroz Recep
机构信息
Department of Molecular Biology and Genetics, Biruni University, Istanbul, Turkiye.
Department of Molecular Biology and Genetics, Van Yuzuncu Yil University, Van, Turkiye.
出版信息
Clin Genet. 2025 Jul;108(1):14-21. doi: 10.1111/cge.14708. Epub 2025 Jan 24.
Inherited retinal diseases (IRDs) constitute a heterogeneous group of clinically and genetically diverse conditions, standing as a primary cause of visual impairment among individuals aged 15-45, with an estimated incidence of 1:2000. Our study aimed to comprehensively evaluate the genetic variants underlying IRDs in the Turkish population. This study included 50 unrelated Turkish IRD patients and their families. Genomic DNA was extracted from each participant, and candidate variants were identified via next-generation sequencing to determine their pathogenicity. We detected variants in 58% of the patients, of which six novel variants were identified. Among these, 16 cases exhibited variants associated with retinitis pigmentosa and Stargardt disease, while 13 presented variants linked to other retinal diseases. The spectrum of identified variants included 21 homozygous cases and five compound heterozygous variants, both indicative of autosomal recessive inheritance. Three cases revealed heterozygous variants suggestive of autosomal dominant inheritance, and two cases featured hemizygous variants suggestive of X-linked inheritance. Importantly, no matches with copy number variants were detected in our analysis. This study comprehensively portrays clinical and genetic profiles within the Turkish population affected by IRDs. Identifying novel variants and delineating inheritance patterns contribute to a deeper understanding of the genetic diagnosis of IRDs, paving the way for more precise diagnostic and therapeutic interventions.
遗传性视网膜疾病(IRDs)是一组临床和遗传上都具有多样性的疾病,是15至45岁人群视力损害的主要原因,估计发病率为1:2000。我们的研究旨在全面评估土耳其人群中IRDs潜在的基因变异。本研究纳入了50名无亲缘关系的土耳其IRD患者及其家属。从每个参与者中提取基因组DNA,并通过下一代测序确定候选变异,以确定其致病性。我们在58%的患者中检测到变异,其中鉴定出6个新变异。其中,16例表现出与色素性视网膜炎和斯塔加特病相关的变异,13例表现出与其他视网膜疾病相关的变异。鉴定出的变异谱包括21例纯合变异和5例复合杂合变异,均表明为常染色体隐性遗传。3例显示提示常染色体显性遗传的杂合变异,2例具有提示X连锁遗传的半合子变异。重要的是,我们的分析中未检测到与拷贝数变异相匹配的情况。本研究全面描绘了受IRDs影响的土耳其人群的临床和遗传特征。鉴定新变异并描绘遗传模式有助于更深入地理解IRDs的基因诊断,为更精确的诊断和治疗干预铺平道路。