Center of Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, 2650 Antwerp, Belgium.
Department of Cardiology, IKEM, Praha 4, 14021 Prague, Czech Republic.
Int J Mol Sci. 2021 Jul 1;22(13):7111. doi: 10.3390/ijms22137111.
Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity and mortality. Loss-of-function variants in , 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 variants, including two missense variants affecting highly conserved amino acids in the catalytic domain and three truncating variants. Connective tissue manifestations are apparent in a substantial fraction of the variant carriers. Some 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 variant. In conclusion, our data demonstrate that loss-of-function variants cause a spectrum of aortic and arterial aneurysmal disease, often combined with connective tissue findings.
胸主动脉瘤和夹层（TAAD）是心血管发病率和死亡率的主要原因。编码细胞外基质交联酶赖氨酰氧化酶的 基因的功能丧失变异已被报道可导致家族性 TAAD。使用下一代 TAAD 基因面板，我们鉴定了另外五个携带 变异的先证者，包括影响催化结构域中高度保守氨基酸的两个错义变异和三个截断变异。在很大一部分变异携带者中明显存在结缔组织表现。一些 变异携带者在生命早期就出现 TAAD，而另一些携带者在高龄时主动脉直径正常。最后，我们鉴定了首例携带 变异的自发性冠状动脉夹层患者。总之，我们的数据表明，功能丧失 变异导致一系列主动脉和动脉瘤疾病，常伴有结缔组织表现。
