Application of Whole Exome and Targeted Panel Sequencing in the Clinical Molecular Diagnosis of 319 Chinese Families with Inherited Retinal Dystrophy and Comparison Study.

Zhizhong Ma,Fengsheng Zhang,Ningning Chen,Likun Wang,Jinlu Zhang,Genlin Li,Lei Wang,Liping Yang

doi:10.3390/genes9070360

Abstract

Inherited retinal dystrophies (IRDs) are a group of clinically and genetically heterogeneous diseases involving more than 280 genes and no less than 20 different clinical phenotypes. In this study, our aims were to identify the disease-causing gene variants of 319 Chinese patients with IRD, and compare the pros and cons of targeted panel sequencing and whole exome sequencing (WES). Patients were assigned for analysis with a hereditary eye disease enrichment panel (HEDEP) or WES examination based on time of recruitment. This HEDEP was able to capture 441 hereditary eye disease genes, which included 291 genes related to IRD. As RPGR ORF15 was difficult to capture, all samples were subjected to Sanger sequencing for this region. Among the 163 disease-causing variants identified in this study, 73 had been previously reported, and the other 90 were novel. Genes most commonly implicated in different inheritances of IRDs in this cohort were presented. HEDEP and WES achieved diagnostic yield with 41.2% and 33.0%, respectively. In addition, nine patients were found to carry pathogenic mutations in the RPGR ORF15 region with Sanger sequencing. Our study demonstrates that HEDEP can be used as a first-tier test for patients with IRDs.

Highlights

Inherited retinal dystrophies (IRDs) are a group of clinically and genetically heterogeneous diseases characterized by progressive degeneration of photoreceptors and/or the retinal pigment epithelial cells
A total of 319 Chinese families with IRD were recruited for this study, including 24 autosomal dominant (AD), 33 autosomal recessive (AR), 11 X-linked, and 251 sporadic cases which included those whose inheritance pattern could not be determined
220 patients were initially diagnosed with retinitis pigmentosa (RP), 37 were diagnosed with cone-rod dystrophy, and 11 were initially diagnosed with Usher syndrome

Summary

Introduction

Inherited retinal dystrophies (IRDs) are a group of clinically and genetically heterogeneous diseases characterized by progressive degeneration of photoreceptors and/or the retinal pigment epithelial cells. IRDs have an incidence rate ranging from 1 in 2000 to 1 in 3000, and affect almost two million people worldwide [1]. The retina is the only affected tissue (non-syndromic forms). In some patients, other tissues may be involved More than 280 genes have been shown to be associated with IRD, and all modes of genetic inheritance are involved. This clinical and genetic heterogeneity hamper the efficiency and dependability of clinical molecular diagnosis of IRD

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