Sahin Ibrahim, Erdem Haktan B, Bahsi Taha, Saat Hanife
Department of Molecular Medicine, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, BHR.
Department of Medical Genetics, University of Health Sciences, Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara, TUR.
Cureus. 2024 Feb 6;16(2):e53742. doi: 10.7759/cureus.53742. eCollection 2024 Feb.
Background Inherited retinal diseases (IRD) represent a prominent etiology of visual impairment on a global scale. The lack of a clear definition of the etiology and genotypic spectrum of IRD is attributed to the significant genetic variability seen. Additionally, there is a scarcity of available data about the correlations between genotypes and phenotypes in this context. This study aimed to clarify the range of mutations and the associations between genotypes and phenotypes in IRD. Methods This cohort consists of 223 patients who have been diagnosed with a range of retinal illnesses, such as retinitis pigmentosa (RP), Stargardt (STGD)/STGD-like disease, Usher syndrome, and Leber congenital amaurosis (LCA). The validation of each mutation and its pathogenicity was conducted by bioinformatics analysis, Sanger sequencing-based co-segregation testing, and computational assessment. The link between genotype and phenotype was analyzed in all patients who possessed mutations as described in the recommendations established by the American College of Medical Genetics. Results A total of 223 cases, comprising Turkish and Syrian families, were examined, revealing the presence of 175 distinct mutations in the IRD gene. Among these mutations, 58 were identified as unique, indicating that they had not been previously reported. A total of 119 mutations were identified to be likely pathogenic, while 104 mutations were classified as pathogenic. The study identified patterns of heredity, namely autosomal recessive, dominant, and X-linked inheritance. Conclusions The findings of this study broaden the clinical and molecular aspects of IRD and further enhance our understanding of its complex nature. The discovery of previously unknown relationships between genetic variations and observable traits, as well as the wide range of genetic variants associated with IRD, significantly contributes to our existing understanding of the diverse phenotypic and genotypic characteristics of IRD. This new information will prove invaluable in facilitating accurate clinical diagnoses as well as personalized therapeutic interventions for individuals affected by IRD.
遗传性视网膜疾病（IRD）是全球范围内视力损害的一个主要病因。IRD病因和基因型谱缺乏明确的定义归因于所观察到的显著遗传变异性。此外，在这种情况下，关于基因型与表型之间相关性的可用数据稀缺。本研究旨在阐明IRD中的突变范围以及基因型与表型之间的关联。
该队列由223例被诊断患有一系列视网膜疾病的患者组成，如色素性视网膜炎（RP）、斯塔加特病（STGD）/类斯塔加特病、Usher综合征和莱伯先天性黑蒙（LCA）。通过生物信息学分析、基于桑格测序的共分离检测和计算评估对每个突变及其致病性进行验证。根据美国医学遗传学学院制定的建议，对所有携带突变的患者分析基因型与表型之间的联系。
共检查了223例病例，包括土耳其和叙利亚家庭，发现IRD基因中存在175种不同的突变。在这些突变中，58种被确定为独特的，表明它们此前未被报道过。共鉴定出119种突变可能具有致病性，而104种突变被归类为致病性突变。该研究确定了遗传模式，即常染色体隐性、显性和X连锁遗传。
本研究的结果拓宽了IRD的临床和分子层面，并进一步加深了我们对其复杂性质的理解。遗传变异与可观察特征之间以前未知关系的发现，以及与IRD相关的广泛遗传变异，显著增进了我们对IRD多样表型和基因型特征的现有认识。这些新信息对于促进对IRD患者的准确临床诊断以及个性化治疗干预将被证明具有极高价值。
