Homozygous Missense Mutation on Exon 22 of PKHD1 Gene Causing Fatal Autosomal Recessive Polycystic Kidney Disease

Abstract Autosomal recessive polycystic kidney disease, described as a congenital hepatorenal fibrocystic syndrome, is a significant inherited cause of end stage renal failure in children with reported incidence of 1 in 20,000 live births. The clinical spectrum is wide. Antenatal findings of echogenic reniform enlarged kidneys associated with evidence of intrauterine renal failure in the form of severe oligoamnios are pathognomonic. Postnatal illness ranges from fatal respiratory failure due to pulmonary hypoplasia in neonates to chronic kidney disease in children, or later presentation of ductal plate malformation and portal hypertension. Advances in genetic diagnostic techniques have allowed recognition of genotypes. We report a novel homozygous missense variant on exon 22 of PKHD1 gene (chr6:51915067G > A; c.2167C > T) that results in the amino acid substitution of cysteine for arginine at codon 723 (p.Arg723Cys). The affected neonate presented with antenatal anhydramnios, classical radiological features, and severe hypoxic respiratory failure likely due to pulmonary hypoplasia and succumbed. The parents were found to be heterozygous carriers. Detection of the specific variant in the proband facilitated prenatal investigation in the next pregnancy.