Familial Hirschsprung Disease
Gene: EDNRBComment when marking as ready: Marked as ready: September 4th 2017.Created: 4 Sep 2017, 11:28 a.m.
Added monogenic-polygenic tag based on co-occuring RET variants reported in PMID:10458491 and 10664228. And co-occuring EDN3 variant reported in PMID:23840513 .Created: 3 Aug 2017, 11:16 a.m.
PMID:10458491 (Sakai et al., 1999) identify point variants in both RET and EDNRB (in the 5'UTR) in a Hirschsprung patient with Down syndrome and suggest that RET and EDNRB may interact in the HSCR phenotype. The 5'UTR variant was also reported in 2 patients in PMID:10664228 (2000).Created: 3 Aug 2017, 11:13 a.m.
PMID:10664228 (2000) report 2 disease-causing variants in EDNRB in sporadic Japanese patients with Hirschsprung disease, including a novel A310T variant.Created: 3 Aug 2017, 11:10 a.m.
Comment on list classification: Updated rating from Amber to Green: Green expert review plus mouse model of colonic aganglionosis plus >3 unrelated cases supporting gene:disease association (e.g. PMID:20009762, 10528251, 25852447, 16618617).Created: 3 Aug 2017, 8:56 a.m.
PMID:10090908 (Auricchio et al 1999) suggest a polygenic interaction between RET and EDNRB in Hirschsprung's disease. However, Lek et al., 2016 (PMID: 27535533) question the validity of the EDNRB variant (S305N) in these patients as a susceptibility allele.Created: 3 Aug 2017, 8:53 a.m.
Comment on publications: Publications include case studies and mouse models.Created: 3 Aug 2017, 8:49 a.m.
Comment on mode of inheritance: Updated MOI to reflect suggestion by expert reviewer, Erwin Brosens. OMIM supports a biallelic and monoallelic MOI.Created: 3 Aug 2017, 8:37 a.m.
Mouse model summarised in PMID:27370713, including Aganglionosis in distal colon.Created: 1 Jun 2017, 3:34 p.m.
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
animal model confirmation. functional test confirming deleterious variantsCreated: 8 May 2017, 10:36 a.m.
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: EDNRB were changed from susceptibility to Hirschsprung disease 2, 600155; Waardenburg syndrome, type 4A, 277580; {Hirschsprung disease, susceptibility to, 2}, 600155; Waardenburg syndrome, type 4A, 277580; Hirschsprung Disease, Recessive; Waardenburg; HSCR (short-segment type); colonic aganglionosis; Shah-Waardenburg syndrome; long-segment Hirschsprung's disease; short-segment Hirschsprung's disease to Waardenburg syndrome, type 4A, OMIM:277580; {Hirschsprung disease, susceptibility to, 2}, OMIM:600155; ?ABCD syndrome, OMIM:600501; Colonic aganglionosis; Shah-Waardenburg syndrome; Long-segment Hirschsprung's disease; Short-segment Hirschsprung's disease
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.
This gene has been classified as Green List (High Evidence).
Phenotypes for EDNRB were set to susceptibility to Hirschsprung disease 2, 600155; Waardenburg syndrome, type 4A, 277580; {Hirschsprung disease, susceptibility to, 2}, 600155; Waardenburg syndrome, type 4A, 277580; Hirschsprung Disease, Recessive; Waardenburg; HSCR (short-segment type); colonic aganglionosis; Shah-Waardenburg syndrome; long-segment Hirschsprung's disease; short-segment Hirschsprung's disease
Publications for EDNRB were set to 28543993; 27370713; 16618617; 20009762; 10528251; 26923755; 25852447
Phenotypes for EDNRB were set to susceptibility to Hirschsprung disease 2, 600155; Waardenburg syndrome, type 4A, 277580; {Hirschsprung disease, susceptibility to, 2}, 600155; Waardenburg syndrome, type 4A, 277580; Hirschsprung Disease, Recessive; Waardenburg; HSCR (short-segment type); colonic aganglionosis; Shah-Waardenburg syndrome
This gene has been classified as Green List (High Evidence).
Phenotypes for EDNRB were set to susceptibility to Hirschsprung disease 2, 600155; Waardenburg syndrome, type 4A, 277580; {Hirschsprung disease, susceptibility to, 2}, 600155; Waardenburg syndrome, type 4A, 277580; Hirschsprung Disease, Recessive; Waardenburg; HSCR (short-segment type); colonic aganglionosis
Mode of inheritance for EDNRB was changed to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for EDNRB were set to 28543993; 27370713; 16618617; 20009762
Mode of inheritance for EDNRB was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for EDNRB were set to susceptibility to Hirschsprung disease 2, 600155; Waardenburg syndrome, type 4A, 277580; {Hirschsprung disease, susceptibility to, 2}, 600155; Waardenburg syndrome, type 4A, 277580; Hirschsprung Disease, Recessive; Waardenburg; HSCR (short-segment type)
EDNRB was added to Familial Hirschsprung Diseasepanel. Source: Illumina TruGenome Clinical Sequencing Services
EDNRB was added to Familial Hirschsprung Diseasepanel. Source: Radboud University Medical Center, Nijmegen
Publications for EDNRB were set to 28543993; 27370713; 16618617
Publications for EDNRB were set to 28543993; 27370713
Publications for EDNRB were set to 28543993
EDNRB was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC
EDNRB was created by rfoulger