Thoracic aortic aneurysm or dissection

Gene: MED12

Comment on list classification: MED12 was previously demoted on the GMS equivalent panel (Thoracic aortic aneurysm and dissection v1.2) due to insufficient evidence. Therefore this gene has been demoted from Green to Red to reflect the most up-to-date knowledge here.
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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: 14 Jul 2021, 10:23 a.m. | Last Modified: 14 Jul 2021, 10:23 a.m.

Panel Version: 1.120

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

Green List (high evidence)

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.

Comment on publications: added publications submitted by reviewer.

Created: 2 May 2017, 10:58 a.m.

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.

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

• PMID: 17369503
• 20630950