Familial Hirschsprung Disease

Gene: EDN3

Green List (high evidence)

EDN3 (endothelin 3)
EnsemblGeneIds (GRCh38): ENSG00000124205
EnsemblGeneIds (GRCh37): ENSG00000124205
OMIM: 131242, Gene2Phenotype
EDN3 is in 5 panels

3 reviews

Rebecca Foulger (Genomics England curator)

Added monogenic-polygenic tag based on co-occuring EDNRB variants reported in PMID:23840513.
Created: 3 Aug 2017, 11:20 a.m.
Comment when marking as ready: Marked EDN3 as ready: August 3rd 2017.
Created: 3 Aug 2017, 8:34 a.m.
Comment on list classification: Updated rating from Amber to Green: Green expert review plus sufficient supporting evidence. >3 unrelated cases of EDN3 variants causing Waardenburg syndrome, type 4 (WS4). Note that WS4 is diagnosed when WS2 is accompanied by Hirschsprung disease. Hirschsprung's disease also occurs in ~16% of patients with congenital central hypoventilation syndrome/CCHS, which is also caused by EDN3 variants.
Created: 3 Aug 2017, 8:34 a.m.
Comment on mode of inheritance: Use the MOI suggested by Expert reviewer, Erwin Brosens. OMIM supports a biallelic and monoallelic MOI.
Created: 3 Aug 2017, 8:32 a.m.
Mouse model summarised in PMID:27370713, including Aganglionosis in distal colon.
Created: 1 Jun 2017, 3:32 p.m.

Erwin Brosens (Erasmus MC)

Green List (high evidence)

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

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

Sumita Chhabra (University of Liverpool / Alder Hey Children's Hospital)

animal model confirmation. functional test confirming deleterious variants
Created: 18 Aug 2017, 10:35 a.m.

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

Details

Mode of Inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Alder Hey - Erasmus MC
Phenotypes
  • susceptibility to Hirschsprung disease 4, 613712
  • {Hirschsprung disease, susceptibility to, 4}, 613712
  • Waardenburg syndrome, type 4B, 613265
  • Hirschsprung Disease, Dominant
  • Waardenburg syndrome
  • WS4B
  • total colonic aganglionosis
  • short-segment Hirschsprung disease
Tags
monogenic-polygenic
OMIM
131242
Clinvar variants
Variants in EDN3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

18 Oct 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

18th October 2017: Revised and approved to Version 1.0 after expert and curator review. An expert list from Mr. Simon Kenny and Professor Robert Hofstra's groups (Alder Hey - Erasmus MC) formed the basis of the original panel. The expert list was then expanded based on a review of literature. Many of the literature genes remain red on the V1.0 panel as they were identified through association studies and/or they represent susceptibility/risk factors for Hirschsprung's disease (HSCR). Sumita Chhabra (Alder Hey) and Erwin Brosens (Erasmus) provided extensive feedback for genes on the panel, together with reviews from Merce Garcia-Barcelo.

3 Aug 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

3 Aug 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

3 Aug 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for EDN3 were set to susceptibility to Hirschsprung disease 4, 613712; {Hirschsprung disease, susceptibility to, 4}, 613712; Waardenburg syndrome, type 4B, 613265; Hirschsprung Disease, Dominant; Waardenburg syndrome; WS4B; total colonic aganglionosis; short-segment Hirschsprung disease

3 Aug 2017, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for EDN3 were set to 28543993; 27370713; 8630502; 8630503; 20583152; 19764030

3 Aug 2017, Gel status: 2

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for EDN3 was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

6 Jun 2017, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for EDN3 were set to susceptibility to Hirschsprung disease 4, 613712; {Hirschsprung disease, susceptibility to, 4}, 613712; Waardenburg syndrome, type 4B, 613265; Hirschsprung Disease, Dominant; Waardenburg syndrome; WS4B

6 Jun 2017, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

EDN3 was added to Familial Hirschsprung Diseasepanel. Source: Illumina TruGenome Clinical Sequencing Services

6 Jun 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

EDN3 was added to Familial Hirschsprung Diseasepanel. Source: Radboud University Medical Center, Nijmegen

1 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for EDN3 were set to 28543993; 27370713

1 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for EDN3 were set to 28543993

8 May 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

EDN3 was created by rfoulger

8 May 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

EDN3 was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC