ClinGen Dosage Sensitivity Curation Page
ZEB2
- Curation Status: Complete
- id: ISCA-31348
- Date last evaluated: 2020-06-24
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about ZEB2 at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/9839
- OMIM: https://omim.org/entry/605802
- Gene Reviews: https://www.ncbi.nlm.nih.gov/books/NBK1116/?term=ZEB2%5Bgenesymbol%5D
- ClinGen Haploinsufficiency Score: 3
- ClinGen Triplosensitivity Score: 0
- ExAC pLI score: 1.0
- See related regions:
- Mowat-Wilson [ZEB2 (ZFHX1B)]
- Haploinsufficiency score: 3
- Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
- Haploinsufficiency Phenotype: MOWAT-WILSON SYNDROME; MOWS
| 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
| 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.