Familial Hirschsprung Disease

Gene: RET

Green List (high evidence)

RET (ret proto-oncogene)
EnsemblGeneIds (GRCh38): ENSG00000165731
EnsemblGeneIds (GRCh37): ENSG00000165731
OMIM: 164761, Gene2Phenotype
RET is in 27 panels

3 reviews

Erwin Brosens (Erasmus MC)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: >3 independent cases of RET genes causing Hirschsprung disease. Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. On the Expert list from Alder-Hey and Erasmus, listed for prior genetic testing in the eligibility statement, and rated green by expert review.
Created: 18 Jul 2017, 3:09 p.m.
'monogenic-polygenic' tag added based on PMID:19040714 showing the presence of both RET and NTRK3 mutations in 2 affected family members.
Created: 5 Jun 2017, 1:54 p.m.
Mouse model summarised in PMID:27370713: Intestinal/colonic aganglionosis.
Created: 1 Jun 2017, 3:37 p.m.
PMID:28274275 (Gui et al., 2017) performed de novo mutation (DNM) screening on 24 HSCR trios. 8 DNMs were found in RET, the main HSCR gene, and they provide a zebrafish model for RET involvement in HSCR.
Created: 1 Jun 2017, 12:55 p.m.
PMID:7581377 (Attie et al 1995) studied 45 sporadic cases and 35 familial cases, and found mutations of the RET gene in 50% of familial HSCR.
Created: 1 Jun 2017, 11:49 a.m.

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

animal model confirmation. functional test confirming deleterious variants
Created: 8 May 2017, 10:36 a.m.

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
  • Alder Hey - Erasmus MC
Phenotypes
  • susceptibility to Hirschsprung disease 1, 142623
  • {Hirschsprung disease, susceptibility to, 1}, 142623
  • Hirschsprung Disease, Susceptibility To, 1, 142623
  • Hirschsprung Disease, Dominant
Tags
monogenic-polygenic
OMIM
164761
Clinvar variants
Variants in RET
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.

18 Jul 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).

18 Jul 2017, Gel status: 3

Set publications

Rebecca Foulger (Genomics England curator)

Publications for RET were set to 28543993; 28274275; 7581377; 27370713; 23084198; 8114938; 8114939

6 Jun 2017, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

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

6 Jun 2017, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

RET was added to Familial Hirschsprung Diseasepanel. Source: UKGTN

6 Jun 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

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

5 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for RET were set to 28543993; 28274275; 7581377; 27370713; 23084198

1 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for RET were set to 28543993; 28274275; 7581377; 27370713

1 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for RET were set to 28543993; 28274275; 7581377

1 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for RET were set to 28543993; 28274275

1 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for RET were set to 28543993

1 Jun 2017, Gel status: 0

Upload gene information

Rebecca Foulger (Genomics England curator)

RET was added to Familial Hirschprungs Diseasepanel. Sources: Eligibility statement prior genetic testing

8 May 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

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

8 May 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

RET was created by rfoulger