HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort.

Malformations of the kidney and lower urinary tract are the most frequent cause of end-stage renal disease in children. Mutations in HNF1Β and PAX2 commonly cause syndromic urinary tract malformation. We searched for mutations in HNF1Β and PAX2 in North American children with renal aplasia and hypodysplasia (RHD) enrolled in the Chronic Kidney Disease in Children Cohort Study (CKiD). We identified seven mutations in this multiethnic cohort (10% of patients). In HNF1Β, we identified a nonsense (p.R181X), a missense (p.S148L), and a frameshift (Y352fsX352) mutation, and one whole gene deletion. In PAX2, we identified one splice site (IVS4-1G>T), one missense (p.G24E), and one frameshift (G24fsX28) mutation. All mutations occurred in Caucasians, accounting for 14% of disease in this subgroup. The absence of mutations in other ethnicities is likely due to the limited sample size. There were no differences in clinical parameters (age, baseline eGFR, blood pressure, body mass index, progression) between patients with or without HNF1B and PAX2 mutations. A significant proportion of North American Caucasian patients with RHD carry mutations in HNF1Β or PAX2 genes. These patients should be evaluated for complications (e.g., diabetes for HNF1Β mutations, colobomas for PAX2) and referred for genetic counseling.