Heterozygous p.R135W missense mutation in a large Han-Chinese family with retinitis pigmentosa and different refractive errors.

Retinitis pigmentosa (RP), the most common type of inherited retinal degeneration causing blindness, initially manifests as severely impaired rod function followed by deteriorating cone function. Mutations in the rhodopsin gene () are the most common cause of autosomal dominant RP (adRP). The present study aims to identify the disease-causing mutation in a numerous, four-generation Han-Chinese family with adRP detected by whole exome sequencing and Sanger sequencing. Afflicted family members present classic adRP along with heterogeneous clinical phenotypes including differing refractive errors, cataracts, astigmatism and epiretinal membranes. A missense mutation, c.403C>T (p.R135W), in the gene was identified in nine subjects and it co-segregated with family members. The mutation is predicted to be disease-causing and results in rhodopsin protein abnormalities. The present study extends the genotype-phenotype relationship between gene mutations and adRP clinical findings. The results have implications for familial genetic counseling, clinical management and developing RP target gene therapy strategies.