Novel lox variants in five families with aortic/arterial aneurysm and dissection with variable connective tissue findings
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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 diam-eters 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.
| Original language | English |
|---|---|
| Article number | 7111 |
| Journal | International Journal of Molecular Sciences |
| Volume | 22 |
| Issue number | 13 |
| ISSN | 1661-6596 |
| DOIs | |
| Publication status | Published - 2021 |
Bibliographical note
Funding Information:
This research was largely supported by funding from the University of Antwerp (Methusalem- OEC grant ?Genomed? FFB190208), the Research Foundation Flanders (FWO, Belgium, G042321N, G040221N, G044720N), the Dutch Heart Foundation (2013T093), the Belgian Cardiac Surgery Foundation and the Marfan Foundation. Dr. Loeys holds a consolidator grant from the European Research Council (Genomia?ERC-COG-2017-771945). Dr. Meester (12X8520N) is post-doctoral FWO fellowsMs. Van Gucht (1S70419N),Ms. Van Den Heuvel (1S81820N) are supported by an FWO PhD fellowship. Dr. Loeys, Dr. Verstraeten and Dr. Kempers are members of the European Reference Network on rare multisystemic vascular disorders (VASCERN?project ID: 769036 partly co-funded by the European Union Third Health Programme). The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608, the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre. Dave Adlam has received funding from Abbott Vascular Inc to support a clinical research fellow, in kind support for SCAD-genetics research from Astra Zeneca Inc and research funding from the same company for unrelated research. He has undertaken consultancy for General Electric Inc to support general research funds. Supported by Ministry of Health of the Czech Republic, grant nr. NV18-02-00237 and 00064203/6003 to M.M and A.K.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- ECM, LDS, LOX, MFS, TAAD
Research areas
ID: 301821366