Thoracic aortic aneurysm and dissection

Gene: MED12

Red List (low evidence)

MED12 (mediator complex subunit 12)
EnsemblGeneIds (GRCh38): ENSG00000184634
EnsemblGeneIds (GRCh37): ENSG00000184634
OMIM: 300188, Gene2Phenotype
MED12 is in 13 panels

9 reviews

Ivone Leong (Genomics England Curator)

Red List (low evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel. Therefore this gene has been demoted from Amber to Red.
Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.
Panel Version: 0.35

James Eden (Manchester)

Red List (low evidence)

Minimal association with TAAD in the literature.
Created: 2 Oct 2019, 11:14 a.m. | Last Modified: 2 Oct 2019, 11:14 a.m.
Panel Version: 0.30

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Lujan-Fryns syndrome 309520; Ohdo syndrome, X-linked 300895; Opitz-Kaveggia syndrome 305450

Publications

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

Red List (low evidence)

There are reports of patients with Lujan-Fryns syndrome and aortic dilation, but these were not patients with MED12 variants. Patients reported with MED12 c.3020A>G did not have aortic involvement.
Created: 18 Sep 2019, 7:54 p.m. | Last Modified: 18 Sep 2019, 7:54 p.m.
Panel Version: 0.30

Rebecca Whittington (South West GLH)

Red List (low evidence)

309520 Lujan-Fryns syndrome - connective tissue disorder with ascending aortic aneurysm, ASD/VSD according to OMIM
Created: 25 Mar 2019, 4:30 p.m.
Khan et al 2016 Clin Med Insights Case Rep 9:115 describes this as being an intellectual disability syndrome with Marfanoid features. Patient has variant c.3020A>G p.Asn1007Ser, which has been reported several times with functional studies. This patient does not have aortic involvement and review of literature suggests that intellectual disability and Marfaniod body habitus are usual features with this variant and not aortic.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Nick Camm (NHS)

Green List (high evidence)

Rebecca Foulger (Genomics England curator)

Comment on phenotypes: 'Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders' phenotype is taken from the name of the Emory gene panel.
Created: 31 Jul 2017, 5 p.m.

Louise Daugherty (Genomics England Curator)

Comment on publications: added publications submitted by reviewer.
Created: 2 May 2017, 10:58 a.m.

Ellen McDonagh (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.
Not on the Inherited Cardiac Condition Genes panel for Familial aortic anuerysm reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.​1007/​s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes.
Created: 19 Feb 2016, 10:58 a.m.

Matina Prapa (Genomics England Curator)

Green List (high evidence)

Links to Lujan–Fryns syndrome with aortic root dilation. Med12 is critical member of the Wnt pathway involved in signalling during heart valve formation and cardiac neural crest development.
Created: 14 Feb 2016, 12:24 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
309520- Lujan-Fryns syndrome

Publications

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Red
  • NHS GMS
  • South West GLH
  • London South GLH
  • South West GLH
  • London South GLH
Phenotypes
  • Lujan-Fryns syndrome, 309520
  • Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders
OMIM
300188
Clinvar variants
Variants in MED12
Penetrance
None
Panels with this gene

History Filter Activity

18 Nov 2019, Gel status: 1

Added New Source, Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to MED12. Source Expert Review Red was added to MED12. Rating Changed from Amber List (moderate evidence) to Red List (low evidence)

18 Apr 2019, Gel status: 2

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: MED12 was added gene: MED12 was added to GMS FTAAD placeholder panel. Sources: Expert Review Amber,London South GLH,South West GLH Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: MED12 were set to Lujan-Fryns syndrome, 309520; Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders