A Novel Missense Mutation (L44V) of PAX2 Associated with Adult-Onset End-Stage Renal Disease and No Syndromic Features.

Paired box (PAX) 2, encoded on chromosome 10 in humans, plays a key role in kidney development. The first 3 exons of the gene are highly conserved among species. PAX2 mutations in autosomal dominant papillorenal syndrome (OMIM #120330) are associated with congenital anomalies of the kidney, urinary tract, and eye. A 37-year-old male was admitted to our transplant center for kidney transplantation due to end-stage renal disease (ESRD) caused by chronic glomerulonephritis. Interestingly, 5 members of his family also suffered from ESRD requiring hemodialysis in adulthood. Other ocular or brain anomalies were not reported in this pedigree. We extracted genomic DNA from buccal swabs or peripheral blood samples from the proband and his family members. We identified a novel heterozygous c.130C>G (p.Leu44Val) missense PAX2 mutation in this family by exome sequencing analysis, which we confirmed by Sanger sequencing in the affected family members. This mutation is located in the N-terminus of the paired box domain of PAX2 and predicted to be a pathogenic mutation by in-silico analysis. We report a novel PAX2 mutation identified by exome sequencing in a family with adult ESRD in the absence of other congenital syndromic features.