Cholestasis

Gene: PSKH1

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cholestasis, progressive familial intrahepatic, 13, MIM# 620962

Green List (high evidence)

4 consanguineous families (out of 279 families) with intrahepatic cholestasis:
-1 patient died at 10mths with cholestasis/liver impairment and kidney impairment
-3 cousins with cholestasis (2 with liver failure needing transplant) and kidney features (2 with kidney failure, 1 with renal echogenicity)
-2 siblings with hepatic fibrosis (1 with unilateral renal agenesis)
-2 siblings with unexplained liver cirrhosis (1 needing transplant) but normal kidney function

WES identified 3 different homozygous variants in PSKH1 (Arg121Trp, Ile126Val, Arg183Cys). Patient fibroblasts displayed abnormal cilia that are long and show abnormal transport. A homozygous Pskh1 mutant mouse faithfully recapitulated the human phenotype and displayed abnormally long cilia. The phenotype could be rationalized by the loss of catalytic activity observed for each recombinant PSKH1 variant using in vitro kinase assays. Human PSKH1 is a poorly understood gene that may play important role in intracellular trafficking, is sensitive to intracellular Ca2+ concentration, and is localized to centrosomes, suggesting a link to cystogenesis.
Sources: Literature

Created: 15 Aug 2024, 10:21 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hepatorenal syndrome, MONDO:0001382

Publications

• PMID: 39132680

Variants in this GENE are reported as part of current diagnostic practice