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.
Amelie Stalke  1 ,  Malte Sgodda  2 ,  Tobias Cantz  2 ,  Britta Skawran  3 ,  Elke Lainka  4 ,  Björn Hartleben  5 ,  Ulrich Baumann  6 ,  Eva-Doreen Pfister  6
Affiliations
  • 1. Pediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany; Department of Human Genetics, Hannover Medical School, Hannover, Germany. Electronic address: [email protected].
  • 2. Translational Hepatology and Stem Cell Biology, Department of Gastroenterology, Hepatology and Endocrinology, REBIRTH-Center for Translational Regenerative Medicine, Hannover Medical School, Hannover, Germany.
  • 3. Department of Human Genetics, Hannover Medical School, Hannover, Germany.
  • 4. Department for Pediatric Nephrology, Gastroenterology, Endocrinology and Transplant Medicine, University Children's Hospital Essen, Essen, Germany.
  • 5. Institute of Pathology, Hannover Medical School, Hannover, Germany.
  • 6. Pediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany.
PMID: 34555379 DOI: 10.1016/j.jpeds.2021.09.019
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.