KIF12 Variants and Disturbed Hepatocyte Polarity in Children with a Phenotypic Spectrum of Cholestatic Liver Disease

J Pediatr. 2022 Jan:240:284-291.e9. doi: 10.1016/j.jpeds.2021.09.019. Epub 2021 Sep 21.

Abstract

KIF12 has been identified as a cholestasis-associated candidate gene. We describe 6 cases from 4 unrelated families with diverse cholestatic phenotypes carrying 2 different homozygous KIF12 truncating variants. Immunofluorescence investigations of paraffin-embedded liver sections suggest that KIF12-associated impaired functional cell polarity may be the underlying cause.

Keywords: autosomal cholestatic liver disease; functional cell polarity; liver cirrhosis; possibly underdiagnosed; wide phenotypic spectrum.

Publication types

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

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cholestasis / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Hepatocytes / metabolism
  • Humans
  • Kinesins / genetics*
  • Liver Diseases / genetics*
  • Male
  • Mutation
  • Whole Genome Sequencing

Substances

  • KIF12 protein, human
  • Kinesins