Genetic investigation of 211 Chinese families expands the mutational and phenotypical spectrum in hereditary retinopathy genes through targeted sequencing technology
Background: Hereditary retinopathy is a significant cause of blindness worldwide. Despite the discovery of many mutations in various retinopathies, a large part of patients remain undiagnosed genetically. Targeted next generation sequencing of the human genome is a suitable approach for retinopathy molecular diagnosis.Methods: We described a cohort of 211 families from central China with various forms of retinopathy, 95 families of which were investigated using NGS multi-gene panel sequencing
... panel sequencing as well as the other 116 patients were LHON suspected tested by Sanger sequencing. We validated the candidate variants by PCR-based Sanger sequencing. We have made comprehensive analysis of the cases through sequencing data and ophthalmologic examination information.Results: The potentially causal mutation was identified in majority of the families with retinopathy (57.9% of 95 families) and Leber hereditary optic neuropathy (LHON) (21.6% of 116 families). The identified mutations (68mutations, 37 of which are novel) of the 95 families spanned 31 known disease genes, about half have not been reported relation to hereditary retinopathy. The NGS panel solution provides 45.3% potential diagnostic rate of the retinopathy families and another 12.6% families detect candidate gene mutations with undefined pathogenicity in this study.Conclusion: Our study showed novel mutations and phenotypic aspects of retinopathy, and demonstrated genetic and clinical heterogeneity of the conditions. Our results illustrated the significance of molecular genetic testing for patients with hereditary retinopathy.