■与300多个基因相关的遗传性视网膜营养不良(IRD)是视网膜疾病的临床和遗传异质性组。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。
■对28例无关患者进行了全外显子组测序。使用美国医学遗传学学会变异解释指南评估变异的潜在致病性,在硅预测工具中,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。
■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,28例患者中有26例(92.9%)检测到CNGA3、RDH5、TULP1、BBS2、BEST1、RS1、GUCY2D。最常见的致病变异是MERTK(10.7%的病例),其次是CDHR1,AIPL1,RDH12,SPATA7,CNGA3,TULP1(7.1%的病例,each).本研究中最常见的变异类型是错义变异(53%),其次是移码(21%),胡说八道(20%),和拼接(6%)。十二种新颖的变体,6个错觉,6个错觉,在十个基因中检测到。色素性视网膜炎是最常见的表型,其次是Leber先天性黑蒙。
■这项研究概述了土耳其IRD患者的致病基因变异。在这项研究中鉴定的变体扩展了IRD基因的变体谱。我们认为结合分子和临床数据来诊断IRD患者至关重要,尤其是随着治疗选择的出现。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.