Case Report: Whole-exome analysis of a child with polycystic kidney disease and ventriculomegaly

Genet Mol Res. 2015 Apr 17;14(2):3618-24. doi: 10.4238/2015.April.17.11.

Abstract

Autosomal recessive polycystic kidney disease (ARPKD) is an inherited ciliopathy leading to progressive kidney and liver disease. Biallelic mutations in the PKHD1 gene underlie this condition. We describe a child with bilaterally enlarged cystic kidneys, portal hypertension, and cerebral ventriculomegaly. Molecular genetic investigations using whole-exome sequencing and confirmation using Sanger sequencing revealed a homozygous pathogenic mutation in PKHD1 underlying the clinical phenotype of ARPKD. Whole-exome data analysis was used to search for additional rare variants in additional ciliopathy genes that may have contributed to the unusual brain phenotype. Aside from a rare hypomorphic allele in MKS1, no other pathogenic variants were detected. We conclude that the homozygous pathogenic mutation in PKHD1 underlies the ciliopathy phenotype in this patient.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Child, Preschool
  • DNA Mutational Analysis / methods
  • Exome / genetics*
  • Female
  • Homozygote
  • Humans
  • Hydrocephalus / genetics*
  • Hydrocephalus / pathology
  • Mutation, Missense*
  • Polycystic Kidney, Autosomal Recessive / genetics*
  • Polycystic Kidney, Autosomal Recessive / pathology
  • Receptors, Cell Surface / genetics*

Substances

  • PKHD1 protein, human
  • Receptors, Cell Surface