Limb disorders

Gene: ERCC4

Green List (high evidence)

Comment on list classification: Changed status from Red to Green due to evidence in the literature

Created: 27 Feb 2017, 9:55 a.m.

Comment on phenotypes: omitted those phenotypes not relevant to this panel ( do not describe anaemia as a clinical outcome), specific mutations in ERCC4 are associated with xeroderma pigmentosum (OMIM: 278760) and XFE progeroid syndrome (OMIM: 610965)

Created: 24 Feb 2017, 3:10 p.m.

Comment on publications: Added PMID: 24027083. In addition to the report of 2 individuals w/FA & biallelic ERCC4 pathogenic variants (PMID:23623386); there was a subsequent paper published a few months later, functional studies identified additional bone-fide FA ERCC4 mutations specifically disrupting interstrand cross-link repair (PMID: 24027083). Also the four variants are confirmed in the Leiden Open Variation Database (Fanconi anemia mutation database).

Created: 24 Feb 2017, 3:10 p.m.

Green List (high evidence)

A third case has been repoted for fanconi anaemia (PMID: 23623389).

Created: 24 Feb 2017, 3:57 p.m.

I don't know

Comment when marking as ready: In biallelic form, sufficient evidence of causation for FA and therefore radial dysplasia is an associated phenotypic feature.

Created: 11 May 2017, 10:13 a.m.

Comment on list classification: 3 cases and functional data supportive of causation.

Created: 11 May 2017, 10:11 a.m.

Only two unrelated patients with the Fanconi presentation (therefore relevant to this panel) both with compound heterozygous mutations (truncating / missense combination) however paper undertook functional validation including abnormal chromosome breakage but cases were ascertained as having Fanconi for inclusion. Therefore I am not certain this is independent functional evidence.

Created: 16 Feb 2017, 4:17 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fanconi anemia, complementation group Q 615272; Xeroderma pigmentosum, group F 278760; Xeroderma pigmentosum, type F/Cockayne syndrome 278760

Publications

• PMID 23623386

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fanconi anemia

Publications

• 23623386

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