KIF12 Variants and Disturbed Hepatocyte Polarity in Children with a Phenotypic Spectrum of Cholestatic Liver Disease - 21/12/21

Doi : 10.1016/j.jpeds.2021.09.019

Amelie Stalke, PhD ^1,^2,^⁎ , Malte Sgodda, PhD ³, Tobias Cantz, MD ³, Britta Skawran, PhD ², Elke Lainka, MD ⁴, Björn Hartleben, MD ⁵, Ulrich Baumann, MD ¹, Eva-Doreen Pfister, MD ¹
¹ Pediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany
² Department of Human Genetics, Hannover Medical School, Hannover, Germany
³ Translational Hepatology and Stem Cell Biology, Department of Gastroenterology, Hepatology and Endocrinology, REBIRTH-Center for Translational Regenerative Medicine, 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

^∗Reprint requests: Amelie Stalke, PhD, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, GermanyHannover Medical SchoolCarl-Neuberg-Strasse 1Hannover30625Germany

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.

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

Abbreviations : ALT, AST, BSEP, CK7, CK19, GGT, HNF1β, KIF12, MDR3, MRP2, OATP1B1, PKD, qRT-PCR, RAB11a, TBP, VIPAS39, VPS33B, ZO-1, ZO-2

Plan

Methods

Exome Sequencing and Variant Classification

Immunohistochemistry

Immunofluorescence

RNA Extraction and Quantitative Real-time PCR

MYO5B Control Patient

Discussion

Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation - project number 433387263 [to A.S.]) and the German Federal Ministry for Education and Research (BMBF) via the Hereditary Intrahepatic Cholestasis Translational Network (HIChol, grant # 01GM1904B [to M.S., A.S., T.C., U.B., and E.-D.P.]). The authors declare no conflicts of interest.

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Vol 240

P. 284 - janvier 2022 Retour au numéro

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KIF12 Variants and Disturbed Hepatocyte Polarity in Children with a Phenotypic Spectrum of Cholestatic Liver Disease - 21/12/21

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