Thoracic aortic aneurysm or dissection (GMS)
Gene: ATP7A
Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel.Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.
Panel Version: 0.35
Definitely associated with Menkes syndrome, no significant association with aortopathy.Created: 2 Oct 2019, 3:49 p.m. | Last Modified: 2 Oct 2019, 3:49 p.m.
Panel Version: 0.32
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Menkes disease 309400; Occipital horn syndrome 304150; Spinal muscular atrophy, distal, X-linked 3 300489
309400 XLR Menkes disease; 304150 Occipital horn syndrome - some overlap with connective tissue disorders. Disorders of copper metabolism with neurological impariment.Created: 25 Mar 2019, 4:30 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
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, 10:53 a.m.
Menkes disease- despite high frequency of ascending aneurysm formation in the "blotchy" mouse (PMID: 3385878), predominant feature in humans is vascular tortuosity rather than true aneurysm formation with only a few case reports in the literature (brachial artery, PMID: 16939759; iliac artery, PMID: 19522551). In a different study of 95 affected individuals, 4 (4.2%) had major congenital heart defects with no evidence of aortic dilatation on echocardiography (PMID: 22134099). Therefore, there is inadequate information at present linking ATP7A to human thoracic aortic disease.
Occipital horn syndrome- Linked to aneurysm of abdominal vessels, hepatic artery, and splenic artery (PMID: 15981243) but again no evidence of thoracic aortic disease.
Created: 11 Feb 2016, 1:49 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
#309400- Menkes disease; #304150- Occipital horn syndrome; #300489- Spinal muscular atrophy, distal, X-linked 3
Publications
gene: ATP7A was added gene: ATP7A was added to GMS FTAAD placeholder panel. Sources: South West GLH,Expert Review Red Mode of inheritance for gene: ATP7A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females