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

• Main Authors: Ilse Van Gucht, Alice Krebsova, Birgitte Rode Diness, Steven Laga, Dave Adlam, Marlies Kempers, Nilesh J. Samani, Tom R. Webb, Ania A. Baranowska, Lotte Van Den Heuvel, Melanie Perik, Ilse Luyckx, Nils Peeters, Pavel Votypka, Milan Macek, Josephina Meester, Lut Van Laer, Aline Verstraeten, Bart L. Loeys
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: International Journal of Molecular Sciences
• Subjects: TAAD; <i>LOX</i>; ECM; MFS; LDS
• Online Access: https://www.mdpi.com/1422-0067/22/13/7111
• ISSN: 1661-6596; 1422-0067

Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity and mortality. Loss-of-function variants in <i>LOX</i>, 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 <i>LOX</i> variants, including two missense variants affecting highly conserved amino acids in the <i>LOX</i> catalytic domain and three truncating variants. Connective tissue manifestations are apparent in a substantial fraction of the variant carriers. Some <i>LOX</i> 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 <i>LOX</i> variant. In conclusion, our data demonstrate that loss-of-function <i>LOX</i> variants cause a spectrum of aortic and arterial aneurysmal disease, often combined with connective tissue findings.