ObjectiveTo analyze the pathogenic genes and clinical phenotypes of a Chinese Han family with autosomal dominant retinitis pigmentosa (ADRP).

MethodsA pedigree investigation study was conducted, and a Chinese Han RP family that underwent genetic counseling in the Henan Provincial People's Hospital in November 2019 was collected.Twenty members of this family from 4 generations, including 9 patients and 11 phenotypically normal individuals, were enrolled.Visual acuity, peripheral visual field test and fundus examination were performed on some family members.Peripheral blood samples were collected from the family members, and DNA was extracted.Exon-targeted sequencing containing 43 genes associated with RP was performed on the proband using the Ion Torrent PGM sequencing platform.The mutations were verified by polymerase chain reaction and Sanger sequencing.Online software was applied to predict the protein function of the variant.The amino acid sequences of the variant loci were compared using the ClustalW2 multiplex alignment program.The pathogenicity of the variant was analyzed according to American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for classification of genetic variant.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Henan Provincial People's Hospital (No.HNEECKY-2019[15]).

ResultsThe family was consistent with autosomal dominant inheritance.The proband, a 26-year-old male, had bilateral night blindness since childhood, with visual acuity of 0.25 in the right eye and 0.5 in the left eye.There was osteoblast-like pigmentation in his both retinas, thinned retinal vessels and pale optic disc.Full-field electroretinogram examination showed reduced scotopic a- and b-wave peaks and severely reduced photopic a- and b-wave peaks.The rest of the family began to develop night blindness when 7 to 10 years old, having complete loss of peripheral vision around 50 years of age, and typical RP changes were found in ophthalmic examination.Genetic testing revealed a heterozygous missense variant c. 982delC (p.L328fs) in exon 5 of the family's rhodopsin ( RHO) gene (NM_000539.3). This variant resulted in the change of 21 amino acids after amino acid 328 in the encoded RHO protein, increasing amino acids in the coding region from 348 to 358 and altering the structure of the RHO protein.The analysis of protein homology sequence alignment between several different species showed that the locus was highly conserved.According to the guidelines of the ACMG criteria and guidelines for classification of genetic variants, the variant was a pathogenic mutation because there were six evidences including one very strong evidence of pathogenicity PVS1, two moderate evidences of pathogenicity PM2 and three supporting evidences of pathogenicity, PP1, PP3 and PP4.

ConclusionsThe c. 982delC variant in the RHO gene is a pathogenic mutation in this pedigree, and this variant is reported for the first time in a Chinese Han family.