Radial dysplasia

Gene: ERCC4

Green List (high evidence)

ERCC4 (ERCC excision repair 4, endonuclease catalytic subunit)
EnsemblGeneIds (GRCh38): ENSG00000175595
EnsemblGeneIds (GRCh37): ENSG00000175595
OMIM: 133520, Gene2Phenotype
ERCC4 is in 19 panels

4 reviews

Louise Daugherty (Genomics England Curator)

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.

Ellen McDonagh (Genomics England Curator)

Green List (high evidence)

A third case has been repoted for fanconi anaemia (PMID: 23623389).
Created: 24 Feb 2017, 3:57 p.m.

Helen Brittain (Genomics England Curator)

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

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fanconi anemia

Publications

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

History Filter Activity

23 May 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

23.05.2017: Panel revised and approved to Version 1.0 after expert review.

22 May 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for ERCC4 were set to Fanconi anemia, complementation group Q, 615272

11 May 2017, Gel status: 4

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

11 May 2017, Gel status: 4

Set Phenotypes

Helen Brittain (Genomics England Curator)

Phenotypes for ERCC4 were set to Fanconi anemia, complementation group Q 615272

11 May 2017, Gel status: 4

Set publications

Helen Brittain (Genomics England Curator)

Publications for ERCC4 were set to 23623386; 24027083; 23623389

11 May 2017, Gel status: 4

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

6 Dec 2016, Gel status: 2

Upload gene information

Rebecca Foulger (Genomics England curator)

ERCC4 was added to Radial dysplasiapanel. Sources: Expert list

18 Oct 2016, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

ERCC4 was added to Radial dysplasiapanel. Source: Radboud University Medical Center, Nijmegen

18 Oct 2016, Gel status: 1

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

ERCC4 was added to Radial dysplasiapanel. Source: UKGTN Model of inheritance for gene ERCC4 was set to BIALLELIC, autosomal or pseudoautosomal

18 Oct 2016, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

ERCC4 was created by rfoulger

18 Oct 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

ERCC4 was added to Radial dysplasiapanel. Sources: Eligibility statement prior genetic testing