Familial Hirschsprung Disease

Gene: ZEB2

Green List (high evidence)

ZEB2 (zinc finger E-box binding homeobox 2)
EnsemblGeneIds (GRCh38): ENSG00000169554
EnsemblGeneIds (GRCh37): ENSG00000169554
OMIM: 605802, Gene2Phenotype
ZEB2 is in 13 panels

3 reviews

Erwin Brosens (Erasmus MC)

Green List (high evidence)

gene name has changed to ZFHX1B
Created: 3 Aug 2017, 6:32 a.m.

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: Marked ZEB2 as ready: July 20th 2017.
Created: 20 Jul 2017, 1:25 p.m.
Comment on phenotypes: 'Mental retardation and distinct facial features, with or without Hirschsprung disease' is a synonym for Mowat-Wilson syndrome (MIM:235730).
Created: 20 Jul 2017, 1:25 p.m.
Comment on mode of inheritance: Updated MOI to 'NOT imprinted' to match review by Erwin Brosens. Monoallelic MOI confirmed by OMIM and G2P.
Created: 20 Jul 2017, 1:22 p.m.
Comment on list classification: Kept rating as Green: Green expert review and ZEB2 was on original Expert list provided by Sumita Chhabra et al. Confirmed DD-G2P gene for Mowat-Wilson syndrome, which can include Hirschsprung phenotype. Listed in Eligibility statement prior genetic testing list plus sufficient cases (>3) supporting gene:disease link.
Created: 20 Jul 2017, 1:21 p.m.
Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by moderate or severe intellectual disability, a characteristic facial appearance, microcephaly, epilepsy, agenesis or hypoplasia of the corpus callosum, congenital heart defects, Hirschsprung disease, and urogenital/renal anomalies.
Created: 20 Jul 2017, 12:52 p.m.
In 4 of 5 patients with Hirschsprung disease associated with microcephaly, mental retardation, epilepsy, and characteristic facial features of Mowat-Wilson syndrome, Wakamatsu et al. (2001, PMID:11279515) identified pathogenic changes in the ZEB2 gene, including 1 deletion and 3 other variants.
Created: 20 Jul 2017, 12:50 p.m.
Added 'cnv' tag based on notes in Expert list submitted by Sumitra Chhabra and colleagues (Alder Hey - Erasmus MC), and PMID:21712996, which shows CNVs at ZEB2 (ZFHX1B) locus that show association with HSCR in combination with other congenital anomalies.
Created: 5 Jun 2017, 1:48 p.m.
Mouse model summarised in PMID:27370713: colonic and partial small intestinal aganglionosis.
Created: 1 Jun 2017, 3:38 p.m.
Comment on publications: Also called ZFHX1B in literature.
Created: 1 Jun 2017, 8:48 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, NOT imprinted
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
  • Eligibility statement prior genetic testing
  • Alder Hey - Erasmus MC
Phenotypes
  • Mowat-Wilson syndrome, 235730
  • Mowat-Wilson Syndrome, 235730
  • MWS
  • Hirschsprung disease
  • Mental retardation and distinct facial features, with or without Hirschsprung disease
Tags
cnv
OMIM
605802
Clinvar variants
Variants in ZEB2
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.

20 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).

20 Jul 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for ZEB2 were set to Mowat-Wilson syndrome, 235730; Mowat-Wilson Syndrome, 235730; MWS; Hirschsprung disease; Mental retardation and distinct facial features, with or without Hirschsprung disease

20 Jul 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for ZEB2 were set to Mowat-Wilson syndrome, 235730; Mowat-Wilson Syndrome, 235730; MWS; Hirschsprung disease; Mental retardation and distinct facial features, with or without Hirschsprung disease

20 Jul 2017, Gel status: 4

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for ZEB2 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 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).

6 Jun 2017, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

ZEB2 was added to Familial Hirschsprung Diseasepanel. Source: Emory Genetics Laboratory

6 Jun 2017, Gel status: 2

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

ZEB2 was added to Familial Hirschsprung Diseasepanel. Source: Illumina TruGenome Clinical Sequencing Services Model of inheritance for gene ZEB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

6 Jun 2017, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

ZEB2 was added to Familial Hirschsprung Diseasepanel. Source: UKGTN

5 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for ZEB2 were set to 11279515; 28543993; 27370713; 21712996

1 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for ZEB2 were set to 11279515; 28543993; 27370713

1 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for ZEB2 were set to 11279515; 28543993

1 Jun 2017, Gel status: 0

Upload gene information

Rebecca Foulger (Genomics England curator)

ZEB2 was added to Familial Hirschprungs Diseasepanel. Sources: Eligibility statement prior genetic testing

18 May 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for ZEB2 were set to 11279515

8 May 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

ZEB2 was created by rfoulger

8 May 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

ZEB2 was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC