Thoracic aortic aneurysm or dissection (GMS)

Gene: ATP7A

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.

Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.

Panel Version: 0.35

Red List (low evidence)

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

Red List (low evidence)

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

• PMID: 3385878
• 16939759
• 19522551
• 22134099
• 15981243