Fetal anomalies
Gene: TWIST2

TWIST2 (twist family bHLH transcription factor 2)
EnsemblGeneIds (GRCh38): ENSG00000233608
EnsemblGeneIds (GRCh37): ENSG00000233608
OMIM: 607556, Gene2Phenotype
TWIST2 is in 8 panels

2 reviews

Ivone Leong (Genomics England Curator)

Comment on phenotypes: Also associated with Focal facial dermal dysplasia 3, Setleis type, OMIM:227260
Created: 2 Aug 2021, 10:27 a.m. | Last Modified: 2 Aug 2021, 10:27 a.m.

Panel Version: 1.699

Created: 2 Aug 2021, 10:27 a.m.
Last Modified: 2 Aug 2021, 10:27 a.m.
Panel version: 1.699

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.
Created: 4 Apr 2019, 2:03 p.m.

Comment on mode of inheritance: Changed MOI from 'both monoallelic and biallelic' to 'monoallelic'. Inheritance is recessive for Focal facial dermal dysplasia 3, Setleis type (MIM:227260) which Deirdre Cilliers notes would not present pre-natally. Inheritance is autosomal dominant for Ablepharon-macrostomia syndrome (MIM:200110) and Barber-Say syndrome (MIM:209885).
Created: 11 Feb 2019, 4:50 p.m.

Comment on list classification: Updated rating from Amber to Green following comment from Deirdre Cilliers (OUH). Originally rated Amber based on multiple ratings for different disorders, but as Deirdre notes: Setleis would not present prenatally. Sufficient cases (>3) of Barber-Say and ablepharon-macrostomia syndrome to support causation.
Created: 11 Feb 2019, 4:46 p.m.

Comment on mode of pathogenicity: Changed MOP to 'Other' based on comment by Deirdre Cilliers: gain of function for Barber-Say and ablepharon-macrostomia syndrome, which are relevant to this fetal panel. As noted in original upload, DD-G2P record a 'loss of function' mechanism for SETLEIS SYNDROME, but this wouldn't present prenatally (see comment from Deirdre Cilliers).
Created: 11 Feb 2019, 4:42 p.m.

Communication from Deirdre Cilliers, Oxford University Hospitals (via email, February 2019): Yes [TWIST2 should be on the Fetal anomalies panel]. Very particular mutations which improve the chance of variant interpretation - gain of function for Barber-Say and ablepharon-macrostomia syndrome. May present with ambiguous genitalia (microarray may identify a male karyotype when thought that female genitalia were seen on scan) or talipes which may be identified, but other features not clear on scan (loss of lateral lower lip). Setleis type of focal facial dermal dysplasia would not present prenatally, although there is a small chance of an incidental finding if this gene is on the panel.
Created: 11 Feb 2019, 4:38 p.m.

'watchlist' tag added to highlight different DD-G2P ratings for this gene.
Created: 8 Nov 2018, 8:51 p.m.

In the original PAGE file: rated as Confirmed for ABLEPHARON MACROSTOMIA SYNDROME, and rated as Probable for SETLEIS SYNDROME. In the original PAGE file, MOP listed as Dominant negative for ABLEPHARON MACROSTOMIA SYNDROME, and listed as LOF for SETLEIS SYNDROME.
Created: 8 Nov 2018, 4:45 p.m.

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.161

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green
PAGE DD-Gene2Phenotype

Phenotypes

Ablepharon-macrostomia syndrome, 200110
Barber-Say syndrome, 209885

Tags

watchlist

OMIM

607556

Clinvar variants

Variants in TWIST2

Penetrance

None

Publications

26119818

Mode of Pathogenicity

Other

Panels with this gene

History Filter Activity

2 Aug 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: TWIST2 were changed from ABLEPHARON MACROSTOMIA SYNDROME; SETLEIS SYNDROME; Ablepharon-macrostomia syndrome, 200110; Barber-Say syndrome, 209885 to Ablepharon-macrostomia syndrome, 200110; Barber-Say syndrome, 209885

11 Feb 2019, Gel status: 3