Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease

Kidney Int. 2010 Feb;77(4):350-8. doi: 10.1038/ki.2009.440. Epub 2009 Nov 25.


The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fetal Diseases / genetics*
  • Fetal Diseases / pathology*
  • Genotype
  • Humans
  • Infant, Newborn
  • Mutation*
  • Phenotype
  • Polycystic Kidney, Autosomal Recessive / genetics*
  • Polycystic Kidney, Autosomal Recessive / pathology*
  • Receptors, Cell Surface / genetics*


  • PKHD1 protein, human
  • Receptors, Cell Surface