Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity and mortality. Loss-of-function variants in LOX, encoding the extracellular matrix crosslinking enzyme lysyl oxidase, have been reported to cause familial TAAD. Using a next-generation TAAD gene panel, we identified five additional probands carrying LOX variants, including two missense variants affecting highly conserved amino acids in the LOX catalytic domain and three truncating variants. Connective tissue manifestations are apparent in a substantial fraction of the variant carriers. Some LOX variant carriers presented with TAAD early in life, while others had normal aortic diameters at an advanced age. Finally, we identified the first patient with spontaneous coronary artery dissection carrying a LOX variant. In conclusion, our data demonstrate that loss-of-function LOX variants cause a spectrum of aortic and arterial aneurysmal disease, often combined with connective tissue findings.
- MeSH
- aneurysma hrudní aorty genetika patofyziologie MeSH
- aorta metabolismus MeSH
- arterie metabolismus MeSH
- disekce aorty genetika patofyziologie MeSH
- dospělí MeSH
- genetická predispozice k nemoci genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- lysyloxidasa genetika metabolismus MeSH
- mutace genetika MeSH
- nemoci pojiva genetika MeSH
- pojivová tkáň metabolismus MeSH
- rodokmen MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH