Identification Of Pathogenic Mutations In Hereditary Retinal Dystrophies Using Targeted Next-Generation Sequencing

Objectives: Hereditary retinal dystrophies(HRDs) are a group of retinal degenerative diseases with significant genetic and clinical heterogeneities. Traditional techniques is challenging for pathogenic mutations. This study was to identify the diseasing-causal genes in 20 Chinese families with a variety of HRDs.Methods:Family histories and ophthalmic examinations were obtained from all participants in 20 sporadic families. Targeted sequence capture array technique with next-generation sequencing(NGS) was performed to detect pathogenic mutations in 163 identified HRD associated genes. Variants detected by NGS were filtered by bioinformatic analysis. Genotype-phenotype correlation was also assessed.Results:We identified 11 families with pathogenic mutations, including 8 compound heterozygous mutations and 3 homozygous mutations, which were not yet reported. These findings showed genetic diagnoses in 11 of 20 families(55%). Among them, through genetic screening analysis of family members, 6 families were autosomal recessive inheritance and 5 were unspecific. Identification of different mutations and divergent phenotypes revealed 5 families were affected with cone-rod dystrophy, 3 with Leber congenital amaurosis,1 with congenital stationary night blindness, 1 with Best vitelliform macular dystrophy and 1 with Stargardt disease.Conclusion:Our study revealed novel HRDs-causing mutations and correlated with different phenotypes. These findings provided insights into understanding the genotype-phenotype correlations in HRDs. We also showed that targeted NGS is an effective approach for the genetic diagnoses of HRDs.