Unveiling the Genetic and Phenotypic Landscape of a Chinese Cohort With Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a type of inherited retinal degeneration (IRD) that typically leads to vision loss in individuals of working age. Currently, over 100 genes and loci, as well as over 1000 individual variants, have been identified in relation to RP. The aim of this study was to investigate the genetic distribution and characteristics of Chinese patients with RP, as well as to describe and analyze the genetic features of the high-frequency variant from the RPGR gene.

A total of 69 Chinese patients diagnosed with RP from 36 families were included in this study. Blood samples were collected, and DNA was extracted for genetic analysis. A custom panel targeting 822 genes associated with RP was designed for next-generation sequencing (NGS) analysis. The sequenced data were processed and analyzed using bioinformatics tools to identify genetic variants. Variant classification followed the guidelines provided by the American College of Medical Genetics and Genomics (ACMG), taking into consideration functional effects, population frequencies, and previous literature reports. Variant validation was performed using Sanger sequencing to confirm the presence of identified variants. The inheritance pattern of RP-associated variants was determined by analyzing the segregation pattern within families. Pedigrees were constructed based on the clinical and genetic information of the participants. Statistical analysis was conducted to summarize the clinical characteristics of the RP patients using descriptive statistics. Ethical considerations were strictly followed throughout the study, with approval obtained from the ethics committee and informed consent obtained from all participants.

Following this, the identified variants were classified and subjected to statistical analysis. A total of 15 candidate genes associated with RP were identified, along with 39 variants, consisting of 36 reported variants and 3 novel variants. The majority of these variants were classified as pathogenic. The most common changes observed in this study were substitutions, followed by missense variants. Genetic analysis indicated that all variants occurred in the exon region. In the RPGR gene, half the variants are located in the ORF15. Gene, with half of variants located in ORF15. The most frequent variant within this group was RPGR NM_001034853.1: c.2236_2237del, which was identified in a large five-generation pedigree. The three novel variants reported in this study include NM_015629.3: c.1168_1169insGATTCAGCCTGGCC of PRPF31, NM_001034853.1: c.3026_3027insAGAGGGAGAGGAAGAAGG and NM_000328.2: c.611T>G of RPGR.

The findings of this study offer valuable insights into the genetic variants responsible for RP in affected individuals, which can be utilized for genetic counseling and diagnosis. This underscores the significance of genetic testing in the management and treatment of RP.