Paediatric disorders - additional genes

Gene: ERCC1

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 12:58 p.m. | Last Modified: 11 Mar 2026, 12:58 p.m.

Panel Version: 7.33

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - 5 unrelated cases with a multisystem phenotype characteristic of a DNA repair disorder which is relevant for inclusion on the Paediatric disorders super panel.

Created: 1 Oct 2025, 11:30 a.m. | Last Modified: 1 Oct 2025, 11:30 a.m.

Panel Version: 7.9

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