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

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> Causative variants in 21 genes, including <i>MERTK</i>, <i>SNRP200</i>, <i>MYO7A</i>, <i>AIPL1</i>, <i>RDH12</i>, <i>OTX2</i>, <i>ADGRV1</i>, <i>RPGRIP1</i>, <i>SPATA7</i>, <i>USH2A</i>, <i>MFSD8</i>, <i>CDHR1</i>, <i>EYS</i>, <i>CACNA1F</i>, <i>CNGA3</i>, <i>RDH5</i>, <i>TULP1</i>, <i>BBS2</i>, <i>BEST1</i>, <i>RS1</i>, <i>GUCY2D</i> were detected in 26 (92.9%) of 28 patients. The most prevalent causative variants were observed <i>MERTK</i> (10.7% of cases), followed by <i>CDHR1</i>, <i>AIPL1</i>, <i>RDH12</i>, <i>SPATA7</i>, <i>CNGA3</i>, <i>TULP1</i> (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. <b><i>Conclusion:</i></b> 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.