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

Amelie Stalke; Malte Sgodda; Tobias Cantz; Britta Skawran; Elke Lainka; Björn Hartleben; Ulrich Baumann; Eva-Doreen Pfister

doi:10.1016/j.jpeds.2021.09.019

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.

Authors

Amelie Stalke¹, Malte Sgodda², Tobias Cantz², Britta Skawran³, Elke Lainka⁴, Björn Hartleben⁵, Ulrich Baumann⁶, Eva-Doreen Pfister⁶

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.

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