Familial Hirschsprung Disease

Gene: ZEB2

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

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.

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