Abstract
BackgroundHereditary retinopathy is a significant cause of blindness worldwide. Despite the discovery of many mutations in various retinopathies, a large number of patients remain genetically undiagnosed. Targeted next-generation sequencing of the human genome is a suitable approach for the molecular diagnosis of retinopathy.MethodsWe describe a cohort of 211 families from central China with various forms of retinopathy; 95 patients were investigated using multigene panel sequencing, and the other 116 with suspected Leber hereditary optic neuropathy (LHON) were tested by Sanger sequencing. The detected variation of targeted sequencing was verified by PCR-based Sanger sequencing. We performed a comprehensive analysis of the cases using sequencing data and ophthalmologic examination information.ResultsPotential causal mutations were identified in the majority of families with retinopathy (57.9% of 95 families) and suspected LHON (21.6% of 116 families). There were 68 variants of a certain significance distributed in 31 known disease-causing genes in the 95 families; 37 of the variants are novel and have not been reported to be related to hereditary retinopathy. The NGS panel solution provided a 45.3% potential diagnostic rate for retinopathy families, with candidate gene mutations of undefined pathogenicity revealed in another 12.6%of the families.ConclusionOur study uncovered novel mutations and phenotypic aspects of retinopathy and demonstrated the genetic and clinical heterogeneity of related conditions. The findings show the detection rate of pathogenic variants in patients with hereditary retinopathy in central China as well as the diversity and gene distribution of these variants. The significance of molecular genetic testing for patients with hereditary retinopathy is also highlighted.
Highlights
Hereditary retinopathy is a significant cause of blindness worldwide
More than half of the patients in this study were suspected of having Leber hereditary optic neuropathy (LHON); direct Sanger sequencing of mitochondrial DNA was performed for some, and next-generation sequencing (NGS) was carried out for the remainder
Subject recruitment In total, 211 Chinese families with retinopathy from central China were recruited for this study, including 116 patients from different families with suspected monocular or binocular LHON and 95 families with other retinopathies
Summary
Hereditary retinopathy is a significant cause of blindness worldwide. Despite the discovery of many mutations in various retinopathies, a large number of patients remain genetically undiagnosed. Hereditary retinopathy is one category of the most common genetic retinal diseases causing blindness [1]. With the popularization and clinical application of gene sequencing technology, an increasing number of disease-causing genes and mutations have been discovered; these genes are mainly expressed in photoreceptor cells and retinal pigment epithelial cells [6]. The study of the genetics of retinopathy is important to enhance our understanding of the molecular aspects of eye development, disease and treatment. We chose a family-based strategy to determine the exact inheritance pattern and recurrence risk in offspring Using such a family-based strategy, we can determine whether phenotype and genotype co-segregate in a family, which helps to estimate the pathogenicity of candidate mutations. Our research will illustrate the importance of targeted NGS in the aetiological detection of hereditary eye diseases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
