4.7 Article

Novel LOX Variants in Five Families with Aortic/Arterial Aneurysm and Dissection with Variable Connective Tissue Findings

期刊

出版社

MDPI
DOI: 10.3390/ijms22137111

关键词

TAAD; LOX; ECM; MFS; LDS

资金

  1. University of Antwerp (Methusalem-OEC grant Genomed) [FFB190208]
  2. Research Foundation Flanders (FWO, Belgium) [G042321N, G040221N, G044720N]
  3. Dutch Heart Foundation [2013T093]
  4. Belgian Cardiac Surgery Foundation
  5. Marfan Foundation
  6. European Research Council [Genomia-ERC-COG-2017-771945]
  7. FWO PhD fellowship [12X8520N, 1S70419N, 1S81820N]
  8. European Reference Network on rare multisystemic vascular disorders (VASCERN-project) [769036]
  9. European Union Third Health Programme
  10. BeatSCAD
  11. British Heart Foundation (BHF) [PG/13/96/30608]
  12. NIHR rare disease translational collaboration
  13. Leicester NIHR Biomedical Research Centre
  14. Abbott Vascular Inc
  15. Ministry of Health of the Czech Republic [NV18-02-00237, 00064203/6003]

向作者/读者索取更多资源

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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据