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Intellectual disability

Gene: TWIST2

Amber List (moderate evidence)

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

5 reviews

Helen Brittain (Genomics England Curator)

Comment on list classification: AR (Setleis) phenotype not typically associated with ID. Monoallelic (Barber-Say syndrome) presents with physical differences and on the whole, normal development. I accept that a handful of patients have been reported with mild delay, but on balance this is not currently appropriate for the ID panel. Reviewed with Arianna Tucci and consensus reached.
Created: 14 Nov 2017, 1:47 p.m.

Arianna Tucci (Genomics England Curator)

Comment when marking as ready: Marked as green as ID is part of the phenotypic specturm
Created: 10 Nov 2017, 3:28 p.m.

Rebecca Foulger (Genomics England curator)

I don't know

Amber rating because ID evidence is indirect: ID/DD is a clinical feature associated with Setleis syndrome (SS, e.g. PMID:4486222); some forms of SS are due to TWIST2 AR variants but some are due to chromosome 1p36.22p36.21 duplications, and literature points to ID presenting in patients with 1p36.22p36.21 duplications. Additionally, mental retardation is listed as in the clinical synopsis for Barber-Say syndrome in some patients (PMID:26119818), which is caused by heterozygous TWIST2 variants. Thirdly, a heterozygous deletion involving HDAC4, TWIST2 and FLJ43879 shows AD inheritance and is reported with ID and DD (PMID:23188045). Further direct evidence required before diagnostic rating. After consultation with Arianna Tucci, updated MOI to both biallelic and monoallelic, because ID can present with Barber-Say syndrome which has AD inheritance, and Setleis syndrome has AR inheritance.
Created: 31 Oct 2017, 9:24 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Barber-Say syndrome, 209885 (includes mental retardation in some patients); Focal facial dermal dysplasia 3, Setleis type, 227260 (can include intellectual disability and developmental delay)

Publications

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 8:50 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Louise Daugherty (Genomics England Curator)

Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to access inclusion and pertinence to this panel.
Created: 28 Jul 2017, 4:57 p.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert Review Amber
Phenotypes
  • Barber-Say syndrome, 209885 (includes mental retardation in some patients)
  • Focal facial dermal dysplasia 3, Setleis type, 227260 (can include intellectual disability and developmental delay)
OMIM
607556
Clinvar variants
Variants in TWIST2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

29 Nov 2017, Gel status: 2

Set mode of inheritance, Set publications

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene TWIST2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene TWIST2 was set to ['26119818']

28 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

27 Jul 2017, Gel status: 0

Created

BRIDGE consortium (NIHRBR-RD)

TWIST2 was created by BRIDGE

27 Jul 2017, Gel status: 0

Added New Source

BRIDGE consortium (NIHRBR-RD)

TWIST2 was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene