Rapid identification of pathogenic mutations in sporadic hereditary retinal dystrophies using targeted next-generation sequencing

Abstract

Background Hereditary retinal diseases (HRDs) are a group of retinal degenerative diseases with significant genetic and clinical heterogeneities.Traditional techniques are challenging for detection of pathogenic mutations. Objective 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 232 identified genes associated with HRDs.Variants detected by NGS were filtered by bioinformatic analysis HRDs.Genotype-phenotype correlation was also assessed. Results We identified 11 patients 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 patients, with the positive rate of 55%.Among them, 6 patients were autosomal recessive inheritance and 5 were unspecific.Identification of different mutations and divergent phenotypes revealed 5 patients were affected with cone-rod dystrophy, 3 patients with Leber congenital amaurosis, 1 patient with congenital stationary night blindness, 1 patient with Best vitelliform macular dystrophy and 1 patient with Stargardt disease. Conclusions Targeted NGS is an effective approach for the genetic diagnoses of HRDs.These findings provide insights into understanding the genotype-phenotype correlations in HRDs. Key words: Hereditary retinal disease; Pathogenic mutations; Target gene capture; Next-generation sequencing