biostudies-literatureVan Gucht IBritish Heart FoundationEuropean Research CouncilUniversiteit AntwerpenFonds Wetenschappelijk OnderzoekNational Institute for Health Research (NIHR)Dutch Heart FoundationEuropean 398 Reference Network on rare multisystemic vascular disorders7111https://www.ebi.ac.uk/biostudies/studies/S-EPMC8269155biostudies-literatureUnknown22(13)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 International journal of molecular sciencesNovel <i>LOX</i> Variants in Five Families with Aortic/Arterial Aneurysm and Dissection with Variable Connective Tissue Findings.PMC8269155PG/13/96/306081S81820N2013T093FFB190208G042321NNF-SI-0611-10170771945ERC-COG-2017-771945)G044720N12X8520N7690361S70419NG040221N,Adlam DMacek MLoeys BLKrebsova AVerstraeten ADiness BRPerik MVotypka PSamani NJVan Laer LMeester JLaga SPeeters NVan Den Heuvel LVan Gucht IKempers MWebb TRLuyckx IBaranowska AAfalseNovel <i>LOX</i> Variants in Five Families with Aortic/Arterial Aneurysm and Dissection with Variable Connective Tissue Findings.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 2021-01-01T00:00:00Z2021 Jul2026-04-08T07:23:04.742Z2026-04-07T23:40:52.6ZS-EPMC82691553428116510.3390/ijms22137111