Schwartzman William E, Hujoel Margaux L A, Channaoui Nadine, Lee-Kim Vivian, Loh Po-Ru, Gupta Rajat M
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Center for Data Sciences, Brigham and Women's Hospital, Boston, Massachusetts, USA.
JACC Case Rep. 2025 Mar 19;30(6 Pt 1):102973. doi: 10.1016/j.jaccas.2024.102973. Epub 2025 Jan 22.
Thoracic aortic aneurysm and dissection (TAAD) is a rare but often fatal vascular disease. A family history of TAAD increases risk, and several genes are linked to risk of both aneurysm and dissection. The current AHA/ACC guidelines for management of TAAD include genetic testing for affected individuals with no other risk factors such as hypertension or bicuspid aortic valve. However, interpretation of genetic testing results, even for validated TAAD genes, can be challenging. Herein we show 2 TAAD cases in patients with MYH11 copy number variations. These cases demonstrate that MYH11 deletion is often miscategorized as pathogenic, while MYH11 duplication is miscategorized as benign. We then confirm the association of chromosome 16p13.1 duplications which include MYH11 and aortic dissection in the UK Biobank clinical registry. These cases underscore the risk of misannotation of MYH11 structural variants in the evaluation of genetic risk for TAAD patients.
胸主动脉瘤和夹层（TAAD）是一种罕见但往往致命的血管疾病。TAAD家族史会增加患病风险，并且有几种基因与动脉瘤和夹层的风险相关。当前美国心脏协会/美国心脏病学会（AHA/ACC）关于TAAD管理的指南包括对没有高血压或二叶式主动脉瓣等其他风险因素的受影响个体进行基因检测。然而，即使对于经过验证的TAAD相关基因，基因检测结果的解读也可能具有挑战性。在此我们展示了2例存在MYH11拷贝数变异的TAAD病例。这些病例表明，MYH11缺失常被错误分类为致病性变异，而MYH11重复则被错误分类为良性变异。然后我们在英国生物银行临床登记处证实了包含MYH11的16号染色体p13.1区域重复与主动脉夹层之间的关联。这些病例强调了在评估TAAD患者遗传风险时MYH11结构变异错误注释的风险。
