Identification of novel RHO homozygous mutation in Chinese autosomal recessive retinitis pigmentosa patients

Abstract Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinal diseases with more than 80 identified causative genes to date. The RHO (rhodopsin, OMIM 180380 ) gene mutation is a hotspot mutation worldwide and is one of the few genes which can cause both autosomal-dominant RP (adRP) and autosomal-recessive RP (arRP). To explore the frequency of RHO mutations in Chinese populations, RP patients’ samples from 72 unrelated Chinese families with uncertain inherited pattern were collected. Testing of RHO was conducted by NGS (next-generation sequencing) and followed by Sanger sequencing validation to determine the responsible mutation. Our results showed that 4 RHO gene mutations were detected in 5 (10.4%) of the 72 RP families, including c.158C > G (p.P53R), c.551A > C (p.Q184P) in 2 families, c.34delC (p.P12NA) and c.82C > T (p.Q28X). The latter 2 mutations were novel. The homozygous c.82C > T (p.Q28X) was responsible for recessive RP, and the heterozygous carriers in that family (father, mother, sister, brother, and elder son) showed no RP phenotype based on fundus, vision field, and electroretinography (ERG) detection. An in vitro function study of RHO mutant (p.Q28X) gene showed no difference at mRNA level as compared to the wild-type RHO and truncated rhodopsin protein (3kD) was translated. In addition, the intracellular distribution pattern of the rhodopsin mutant (c.82C > T) mainly localized to the cytoplasma and the nucleus, while wild-type rhodopsin was mainly localized near the plasma membrane. Our results showed that not only was the RHO gene mutation the most frequent one among these 72 Chinese RP patients, but also the 2 newly identified mutations expanded the RHO mutation spectrum. The RHO homozygous mutant (p.Q28X) forms truncated rhodopsin protein to induce RP.