Abstract
Purpose :
Autosomal dominant retinitis pigmentosa (adRP) is a genetically heterogeneous disorder for which 29 genes have been reported to be mutated. The objectives of this study were to unravel the molecular basis and assess the contribution of the genes underlying their condition in Chinese patients with possible adRP.
Methods :
A total of 104 probands with clinical diagnosis of RP and suspected autosomal dominant inheritance were recruited for genetic analysis. All probands underwent ophthalmic examinations. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger–DNA sequencing, and multiplex ligation probe amplification assay, was used to detect single-nucleotide variants and copy number variation (CNV).
Results :
We identified pathogenic or possible pathogenic mutations in 67 families, giving a detection rate 64%. Overall, 58 distinct disease-causing mutations involving 13 adRP genes, 2 X-linked RP genes, and 1 Wagner syndrome gene were identified, and 34 were novel. Mutations of RHO were most frequent and responsible for 20.2% (21/104) of the adRP families. Mutations of four splicing factor genes were account for 26% (27/104) of the adRP families, including mutations of PRPF31 (12.9%), SNRNP200 (7.7%), PRPF8 (3.8 %), and PRPF6 (1.0%) (Figure). Missense mutations were most frequently identified in adRP genes, however, majority mutations detected in PRPF31 were null mutations containing four distinct CNVs.
Conclusions :
Our results indicate that mutations in RHO and the pre-mRNA splicing-factor genes are major causes of Chinese Families with adRP. CNVs of PRPF31 account for certain proportions of mutations. Combining multiple screening strategy may increase the detection rate for adR
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.