ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
16053902 Zweier et al., (2005) identified small deletions, splice site or truncating variants of ZEB2 (also known as ZFHX1B) using FISH, qPCR and sequencing. in 28 patients classified as typical Mowat-Wilson syndrome (MOWS). Zweier et al., (2003) (PMID: 12920073) previously identified variable sizes of deletions involving ZEB2 (from 300 kb to 11 Mb) in four patients with clinical features of MOWS.
15121779 Ishihara et al., (2004) described 0.2?10.42 Mb deletions of 2q22?q24.1, including partial or entire ZEB2, using a multiplex PCR method in eight patients. The authors also identified five novel nonsense and frameshift variants of ZEB2 in patients with MOWS.
19842203 Saunderset al., (2009) reported haploinsufficiency of ZEB2 in 27 patients with MOWS from a North American Cohort. Twenty-one patients had a nonsense, frameshift, or splice site variant identified by sequencing. Six patients had partial or entire deletions of ZEB2

Haploinsufficiency phenotype comments:

Haploinsufficieny of ZEB2 (also known as ZFHX1B) is associated with autosomal dominant Mowat-Wilson syndrome (MOWS) characterized by distinctive facial features, intellectual disability, delayed motor development, epilepsy, and various structural anomalies including: Hirschsprung disease, genitourinary anomalies, congenital heart defects, and agenesis or hypogenesis of the corpus callosum. Wenger et al., (PMID: 25123255) described de novo variants of ZEB2 in 27/28 patients (parental testing not available for patient 28). Among the 28 patients, 22 had de novo loss of function variants. Other related publications: PMID: 24715670; PMID: 25326637; PMID: 31564432; PMID: 29455050

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Evidence for triplosensitivity phenotype
PubMed ID Description
29263819 Mak et al., (2016) described a 2 Mb duplication of 2q22.3 overlapping entire ZEB2 (in addition to two other genes) in a patient with conotruncal heart disease.

Triplosensitivity phenotype comment:

Triplosensitivity of ZEB2 has not yet been characterized in an established clinical phenotype.