40 Retinitis Pigmented Families-Study on Pathogenic Mutagenesis and Molecular Diagnosis Based on Target Capture Next Generation Sequencing Technology

Abstract

Purpose : Retinitis pigmentosa (RP) is a progressive, hereditary, and malnutritional degenerative disease with a prevalence of about 1 in 3000-5000. RP has a high degree of genetic heterogeneity, diverse and non-specific clinical features, which is difficult to identify the type of disease and the pathogenesis of the disease only by the clinical manifestations. Recently, the development of target capture-next generation sequencing(NGS) technology has been favored with its high throughput, wide scale and low cost, and the purpose of our study was to detect pathogenic mutations of RP by the technology.

Methods : The target capture-NGS technology was used to detect pathogenic mutations in 40 RP families for 1651 gene of ophthalmic inherited disease (including 261 gene related with retinal disease and 63 gene related with RP) and analyzed the relationship between phenotypes and genotypes. Sanger sequencing was used to validate the candidate pathogenic mutations which were validated in families, respectively.

Results : A detection rate of 60.7% was achieved including mutations in 63 known gene causing RP. A total of 46 distinct mutations were identified, including 22 novel mutations. We found the USH2A(32%), RHO(6%), BBS1(4%),and PRPF8(4%), RPGR(4%),CYP4V2(4%),PDE6B(4%) were high frequency of mutations in Chinese retinal pigmentosa disease. We also identified three de novo mutation in RHO, PRPH8, FSCN2 in 3 RP cases.

Conclusions : The target capture-NGS technology can improve the detection rate of pathogenic genes in RP patients and provide important technical means for further exploration of the molecular genetic etiology and pathogenic mechanism of RP. Our results could enrich the mutation spectrum and gene prevalence for RP and provide the theoretical basis of clinical molecular diagnosis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.