PDF(Pubmed)
Abstract：
Nonsyndromic sporadic thoracic aortic aneurysm (nssTAA) is characterized by diverse genetic variants that may vary in different populations. Our aim was to identify clinically relevant variants in genes implicated in hereditary aneurysms in Russian patients with nssTAA. Forty-one patients with nssTAA without dissection were analyzed. Using massive parallel sequencing, we searched for variants in exons of 53 known disease-causing genes. Patients were found to have no (likely) pathogenic variants in the genes of hereditary TAA. Six variants of uncertain significance (VUSs) were identified in four (9.8%) patients. Three VUSs [FBN1 c.7841C>T (p.Ala2614Val), COL3A1 c.2498A>T (p.Lys833Ile), and MYH11 c.4993C>T (p.Arg1665Cys)] are located in genes with \"definitive\" disease association (ClinGen). The remaining variants are in \"potentially diagnostic\" genes or genes with experimental evidence of disease association [NOTCH1 c.964G>A (p.Val322Met), COL4A5 c.953C>G (p.Pro318Arg), and PLOD3 c.833G>A (p.Gly278Asp)]. Russian patients with nssTAA without dissection examined in this study have ≥1 VUSs in six known genes of hereditary TAA (FBN1, COL3A1, MYH11, NOTCH1, COL4A5, or PLOD3). Experimental studies expanded genetic testing, and clinical examination of patients and first/second-degree relatives may shift VUSs to the pathogenic (benign) category or to a new class of rare \"predisposing\" low-penetrance variants causing the pathology if combined with other risk factors.
摘要：
非综合征性散发性胸主动脉瘤（nssTAA）的特征是不同的遗传变异，可能在不同人群中有所不同。我们的目的是确定与俄罗斯nssTAA患者的遗传性动脉瘤有关的基因中的临床相关变异。分析41例无夹层的nssTAA患者。使用大规模平行测序，我们搜索了53个已知致病基因的外显子中的变异。发现患者在遗传性TAA基因中没有（可能）致病性变异。在4例（9.8％）患者中发现了6种不确定意义的变异（VUS）。三个VUS[FBN1c.7841C>T（p。Ala2614Val),COL3A1c.2498A>T（p。Lys833Ile)，和MYH11c.4993C>T（p。Arg1665Cys）]位于具有“确定性”疾病关联（ClinGen）的基因中。其余的变体在“潜在诊断”基因或具有疾病关联的实验证据的基因中[NOTCH1c.964G>A（p。Val322Met），COL4A5c.953C>G（p。Pro318Arg),和PLOD3c.833G>A（p。Gly278Asp)].在本研究中检查的未经解剖的nssTAA的俄罗斯患者在遗传性TAA的六个已知基因（FBN1，COL3A1，MYH11，NOTCH1，COL4A5或PLOD3）中具有≥1个VUS。实验研究扩大了基因检测，患者和一级/二级亲属的临床检查可能会将VUS转移到致病性（良性）类别或新类别的罕见“易感”低外显率变异，如果与其他危险因素结合，则会导致病理。
