Neonatal onset Autosomal Dominant Polycystic Kidney Disease (ADPKD) in a patient homozygous for a PKD2 missense mutation due to uniparental disomy

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by progressive development of fluid-filled cysts in both kidneys. Cyst formation causes chronic renal failure beyond mid-life eventually leading to end-stage renal failure. Heterozygous mutations in the polycystic kidney disease 1 (PKD1) gene and polycystic kidney disease 2 (PKD2) gene account for almost all cases and although the clinical manifestations overlap, a mutation in PKD2 is associated with a milder disease than a mutation in PKD1. Recently, several PKD1-patients have been described with severe (in utero) renal cystic disease due to a second PKD1-mutation that mildly reduces function of the protein or carrying two of those mild PKD1-mutations. At a heterozygous state they produce no or a very mild phenotype.  Here, we report for the first time a patient with neonatal-onset of PKD caused by a homozygous PKD2 missense mutation.  The mutation is inherited from the mother who carries one mutation and does not have renal cystic disease. Due to a complex genomic rearrangement (uniparental disomy)  the mutation is transmitted on both chromosomes 4. (By Dr. Dorien Peters, http://jmg.bmj.com/content/early/2011/11/22/jmedgenet-2011-100452.abstract?papetoc )