Genotype-phenotype analysis in patients with PAX2 mutations: beyond renal coloboma syndrome

Abstract PAX2 -related disorders encompass renal coloboma syndrome (RCS) and hereditary focal segmental glomerulosclerosis (FSGS)type 7. In this multicenter study on patients with PAX2 mutations, we explored genotype-phenotype correlations regarding kidney and ocular involvement and long-term clinical outcomes. Among 27 patients with PAX2 mutations detected from 2004–2022, 19 had RCS, 4 had FSGS, and 4 had isolated congenital anomalies of the kidneys and urinary tract (CAKUT). Based on genotypes, patients were classified into truncating (n=22) and missense (n=5) mutation groups. Truncating mutations were associated with RCS in 81.8% of cases, while missense mutations were linked to FSGS (n=2) and isolated CAKUT (n=2) in 80.0% of cases ( P =0.034). Fourteen patients developed kidney failure at a median age of 14.5 years, with no difference in kidney survival between the truncating and missense mutation groups. However, mutations in the paired domain of PAX2 resulted in kidney failure more rapidly than mutations in other sites ( P =0.025). Regarding ocular manifestations, the truncating mutation group exhibited more common, earlier onset and severe involvement compared to the missense mutation group. Our findings support genotype-phenotype correlations in ophthalmology field and emphasize the impact of the paired domain on kidney outcomes in patients with PAX2 mutations.