关键词: 真性小眼球, PRSS56基因突变

Abstract: Objective To explore the genetic and clinical characteristics of PRSS56 gene mutations in Chinese patients with nanophthalmos and to reveal correlations between genotypes and phenotypes. Design Retrospective case series. Participants Forty unrelated Chinese families with nanophthalmos, diagnosed and followed up at Beijing Tongren Hospital from 2003 to 2023. Methods Comprehensive ophthalmic examinations were performed on the patients and their family members. Peripheral venous blood was collected from 51 patients and 42 family members with normal ocular phenotypes. DNA was extracted, and the coding region and adjacent intron regions of the PRSS56 gene were analyzed by whole-exome sequencing (WES), followed by bioinformatics analysis and pathogenicity prediction. Statistical analysis of genotypes and phenotypes was conducted using SPSS 27.0 and R 4.4.1 software. Main Outcome Measures Ophthalmic examination results, mutant genotypes, and the proportion of complications such as angle-closure glaucoma (ACG) and uveal effusion syndrome (UES). Results PRSS56 gene mutations were identified in 15 of 40 unrelated Chinese nanophthalmos families (15 probands and 5 affected family members ), with a detection rate of 37.50%. A total of 16 PRSS56 gene mutations were discovered, including 3 novel mutations [c.494dupG (p.Glu167Gly), c.340dupG (p.Ala115Gly), c.407C>T (p.Ala136Val)] and 13 previously reported mutations. Among these, the mutation frequency of c.1066dupC was 53.33% (8/15), making it the most common mutation in this cohort. Nanophthalmos patients with PRSS56 gene mutations exhibited typical clinical features of poor vision, short axial length, and shallow anterior chamber, accompanied by optic disc crowding, tortuous and dilated retinal vessels, and retinal folds in the macular area. Patients first diagnosed after the age of 40 years had a thicker average scleral thickness, a shallower average central anterior chamber depth, and higher proportion of ACG and UES( all P<0.05). The group carrying the high-frequency mutation of c.1066dupC showed a tendency of having a shorter anterior segment. Conclusion This study elucidates the PRSS56 gene mutations and clinical characteristics in Chinese patients with nanophthalmos and their correlations, expands the mutation spectrum of the PRSS56 gene, deepens the understanding of genotype-phenotype correlations in nanophthalmos, and lays a more comprehensive theoretical foundation for the accurate diagnosis, treatment, and prognostic management of this disease. (Ophthalmol CHN, 2025, 34: 27-33)

Key words: nanophthalmos, PRSS56 gene mutations