Cholestasis

Gene: ERCC1

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - liver dysfunction was reported in all affected individuals with ERCC1-hepatorenal syndrome, with three children requiring liver transplants.

Progressive cholestatic liver disease was found in 3 individuals (PV50LD, PV46LD, XE28CH). Individual CA16LD also developed neonatal cholestasis which resolved, and XE1AH developed liver disease later than others in the cohort but showed signs suggestive of chronic cholestatic disease (PMID: 40684071)

Created: 1 Oct 2025, 11:28 a.m. | Last Modified: 1 Oct 2025, 12:41 p.m.

Panel Version: 3.10

ERCC1 is associated with a spectrum of DNA repair disorders from severe neonatal conditions (Cerebrooculofacioskeletal syndrome 4, OMIM:610758) to multisystem disorders (Xeroderma Pigmentosum) that can extend into adolescence and early adulthood.

A recent study (PMID: 40684071) identified seven individuals from five families carrying biallelic ERCC1 variants, who exhibited a distinct clinical phenotype including growth restriction, photosensitivity, and kidney and liver dysfunction. Hepatocellular carcinoma developed in four children, resulting in death in two. Older individuals exhibited additional features, including ataxia, basal cell carcinomas, pancreatic insufficiency, ovarian failure, hypothyroidism, and restrictive lung disease. Most reported individuals have c.466 C > T (p.Arg156Trp) on at least one allele, often with a LOF variant in trans. Functional assays using patient-derived fibroblasts demonstrated significant destabilisation of the ERCC1-XPF complex and defects in NER and ICL repair.
Sources: Literature

Created: 1 Oct 2025, 11:17 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
hepatorenal syndrome, MONDO:0001382

Publications

• 40684071