Evaluation of the genetic association between early-onset primary angle-closure glaucoma and retinitis pigmentosa

Primary angle-closure glaucoma (PACG) and retinitis pigmentosa (RP) can co-occur, but the mechanism of their association is not yet established. The purpose of this study was to investigate the differences in ocular biometry parameters and molecular genetics in patients with PACG with or without RP, and to determine the association between PACG and RP. Patients with early-onset PACG (age of onset <45 years) with or without RP were selected from the glaucoma outpatient department after full ocular examinations by the same glaucoma specialist (LX). Ocular biometry parameters were statistically analyzed. Blood samples were collected from the probands, and genomic DNA was sent out for whole exome sequencing. Variants in 326 selected genes, were extracted from the whole exome sequencing data and filtered using multiple bioinformatics analysis. The 326 genes included 10 PACG-associated genes from two genome wide association studies; 45 genes associated with anterior segment dysgenesis, microcornea, and microphthalmia; and 271 RetNet genes. Potential pathogenic variants (PPV) were obtained and underwent further genotype-phenotype analysis. As a result, a total of 32 probands with early-onset PACG were collected; nine had accompanying RP. No significant differences were noted for ocular biometry parameters between patients with PACG with RP and with PACG alone. Systematic analysis of the variants revealed that 16 of 32 probands (50%) carried PPV in 15 of 326 genes, including 14 RetNet genes and one anterior segment dysgenesis-associated gene. Of these 16 probands with PPV, five (55.56%) were from the group of nine probands with both had PACG and RP and 11 (47.83%) were from the group of 23 probands with PACG alone. Of the 15 genes, five genes, CRB1, COL2A1, RHO, RP1L1, and PAX6, were reported to cause phenotypes including glaucoma. The variants in RetNet genes appeared to be associated with a significant proportion of PACG, especially in probands with both PACG and RP. These findings enrich the phenotype spectrum of RetNet genes and provide clues for genetic screening for glaucoma. Our study suggests a genetic association between PACG and RP, although the cause-effect relationship between them needs further validation.