Table 1.
Genes associated with TAA/D (syndromic and non-syndromic).
| Biological Process/Cellular Compartment | Gene | Protein | OMIM | Syndromic TAA/D | Non-Syndromic FTAA/D | Associated Syndrome/Diseases |
|---|---|---|---|---|---|---|
| Extracellular matrix/remodeling | BGN | Biglycan | 300,989 | + | − | Meester-Loeys syndrome. ARD, TAAD, pulmonary artery aneurysm, IA, arterial tortuosity [19]. |
| COL3A1 | Collagen Type III α1 Chain | 130,050 | + | − | EDS, vascular type IV. TAAD, early aortic dissection, visceral arterial dissection, vessel fragility [20]. | |
| EFEMP2 | EGF Containing Fibulin Extracellular Matrix Protein 2 | 614,437 | + | − | Cutis laxa, AR type Ib. Ascending aortic aneurysms, other arterial aneurysms, arterial tortuosity, stenosis [21]. | |
| ELN | Elastin | 123,700 185,500 |
+ | − | Cutis laxa. AD ARD, ascending aortic aneurysm and dissection [22], TAA [23,24], BAV, IA possibly associated with SVAS. | |
| FBN1 | Fibrillin-1 | 154,700 | + | + | Marfan syndrome. ARD, TAA [25], TAAD [26], AAA, other arterial aneurysms, pulmonary artery dilatation, arterial tortuosity [27]. | |
| LOX | Protein-lysine 6-oxidase | 617,168 | − | + | AAT10. AAA, hepatic artery aneurysm, BAV, CAD, TAAD [28,29]. | |
| MFAP5 | Microfibril Associated Protein 5 | 616,166 | − | + | AAT9. ARD, TAA [30,31]. | |
| Smooth muscle cells | ACTA2 | Smooth muscle α-actin | 611,788 613,834 614,042 |
+ | + | AAT6, multisystemic smooth muscle dysfunction, MYMY5. Early aortic dissection, CAD, stroke (moyamoya disease), PDA, pulmonary artery dilation, BAV, TAAD, TAA [24,32]. |
| FLNA | Filamin A | 300,049 | + | − | Periventricular nodular heterotopia and otopalatodigital syndrome. Aortic dilatation/aneurysms, peripheral arterial dilatation, PDA, IA, BAV, TAA [32,33]. | |
| MYH11 | Smooth muscle myosin heavy chain | 132,900 | − | + | AAT4. PDA, CAD, peripheral vascular occlusive disease, carotid IA, TAAD, early aortic dissection [32,34,35]. | |
| MYLK | Myosin light chain kinase | 613,780 | − | + | AAT7. TAAD, early aortic dissections [36,37]. | |
| TGF-β signaling | LTBP1 | Latent TGF-β binding protein 1 | 150,390 | + | − | Aortic dilation with associated musculoskeletal findings. Dental anomalies, short stature. TAAD, AAA, visceral and peripheral arterial aneurysm [38]. |
| LTBP3 | Latent TGF-β binding protein 3 | 602,090 | ||||
| SMAD2 | SMAD2 | 619,657 619,656 |
+ | - | Unidentified CTD with arterial aneurysm/dissections. ARD, ascending aortic aneurysms, vertebral/carotid aneurysms and dissections [39], AAA. | |
| SMAD3 | SMAD3 | 613,795 | + | + | LDS type III. ARD, TAAD [40], early aortic dissection [39], AAA, arterial tortuosity, other arterial aneurysms/dissections [9], IA, BAV. | |
| SMAD4 | SMAD4 | 175,050 | + | - | JP/HHT syndrome. ARD, TAAD [39], AVMs, IA. | |
| SMAD6 | SMAD6 | 602,931 | - | + | AOVD2. BAV/TAA [24]. | |
| TGFB2 | TGF-β2 | 614,816 | + | + | LDS type IV. ARD, TAA [40], TAAD, arterial tortuosity [39], other arterial aneurysms, BAV. | |
| TGFB3 | TGF-β3 | 615,582 | + | - | LDS type V. ARD, TAAD, AAA/dissection, other arterial aneurysms, IA/dissection [39]. | |
| TGFBR1 | TGF-β receptor type 1 |
609,192 | + | + | LDS type I+AAT5. TAAD [40], early aortic dissection, AAA, arterial tortuosity, other arterial aneurysms/dissection [9], IA, PDA, BAV. | |
| TGFBR2 | TGF-β receptor type 2 |
610,168 | + | + | LDS type II+AAT3. TAAD [40], early aortic dissection, AAA, arterial tortuosity, other arterial aneurysms/dissection [9], IA, PDA, BAV. | |
| Others | AXIN1/PDIA2 locus | − | − | + | − | BAV. BAV/TAA [41]. |
| FBN2 | Fibrillin-2 | 121,050 | + | − | Contractual arachnodactyly. Rare ARD and aortic dissection [42], BAV, PDA. | |
| FOXE3 | Forkhead box 3 | 617,349 | − | + | AAT11. TAAD [30] (primarily type A dissection). | |
| MAT2A | Methionine adenosyl-transferase II α | n.a. | − | + | FTAA Thoracic aortic aneurysms [30,43]. BAV. | |
| NOTCH1 | NOTCH1 | 109,730 | − | + | AOVD1. BAV/TAAD [24]. | |
| PRKG1 | Type 1 cGMP-dependent protein kinase | 615,436 | − | + | AAT8. TAAD [28,43], early aortic dissection, AAA, coronary artery aneurysm/dissection, aortic tortuosity, small vessel, CVD. | |
| ROBO4 | Roundabout guidance receptor 4 | 607,528 | − | + | BAV. BAV/TAA [24]. | |
| SKI | Sloan Kettering proto-oncoprotein | 182,212 | + | − | Shprintzen–Goldberg syndrome. ARD, arterial tortuosity, pulmonary artery dilation, other (splenic) arterial aneurysms [36]. | |
| SLC2A10 | Glucose transporter 10 | 208,050 | + | − | Arterial tortuosity syndrome. ARD, ascending aortic aneurysms [36], other arterial aneurysms, arterial tortuosity [44], elongated arteries, aortic/pulmonary artery stenosis. |
In bold: genes associated with dissection. AAA: abdominal aortic aneurysm; AAT/TAA: aortic aneurysm, thoracic; AD: autosomal dominant; AOVD: aortic valve disease; ARD: aortic root dilatation; AVM: arteriovenous malformation; BAV: bicuspid aortic valve; CAD: coronary artery disease; CTD: connective tissue disease; CVD: cerebrovascular disease; EDS: Ehlers-Danlos syndrome; FTAA: familial thoracic aortic aneurysm; FTAAD: familial thoracic aortic aneurysm and/or dissection; HHT: hereditary hemorrhagic telangiectasia; IA: intracranial aneurysm; JP: juvenile polyposis; LDS:, Loeys-Dietz syndrome; n.a.: not applicable; PDA: patent ductus arteriosus; SVAS: supravalvular aortic stenosis; TGF: transforming growth factor; TAAD: thoracic aortic aneurysm and/or dissection.