期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 13, 页码 -出版社
MDPI
DOI: 10.3390/ijms22137111
关键词
TAAD; LOX; ECM; MFS; LDS
资金
- University of Antwerp (Methusalem-OEC grant Genomed) [FFB190208]
- Research Foundation Flanders (FWO, Belgium) [G042321N, G040221N, G044720N]
- Dutch Heart Foundation [2013T093]
- Belgian Cardiac Surgery Foundation
- Marfan Foundation
- European Research Council [Genomia-ERC-COG-2017-771945]
- FWO PhD fellowship [12X8520N, 1S70419N, 1S81820N]
- European Reference Network on rare multisystemic vascular disorders (VASCERN-project) [769036]
- European Union Third Health Programme
- BeatSCAD
- British Heart Foundation (BHF) [PG/13/96/30608]
- NIHR rare disease translational collaboration
- Leicester NIHR Biomedical Research Centre
- Abbott Vascular Inc
- Ministry of Health of the Czech Republic [NV18-02-00237, 00064203/6003]
This study found that patients with LOX gene variants have a spectrum of aortic and arterial aneurysmal diseases, often combined with connective tissue abnormalities. Some patients developed TAAD in early life, while others had normal aortic diameters in advanced age.
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.
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