Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China

Background: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening pathology that remains a challenge worldwide. Up to 40% of TAAD cases are hereditary with complex heterogeneous genetic backgrounds. The purposes of this study were to determine the diagnostic rate of patients with TAAD, investigate the molecular pathologic spectrum of TAAD by next-generation sequencing (NGS), and explore the future preclinical prospects of genetic diagnosis in patients at high-risk of study. Methods: NGS was used to screen 15 genes associated with genetic TAAD in 212 patients from northwestern China. Clinical data of patients were gathered by electrocardiography, transthoracic echocardiography, and computed tomography. Results: Of the 212 patients, 67 (31.60%) tested positive for a (likely) pathogenic variant, 42 (19.81%) had a variant of uncertain significance (VUS), and 103 (48.58%) had no variant (likely benign/benign/negative). A total of 135 reportable variants were detected in our test, among which 77 (57.04%) are first reported in this paper. A genotype-phenotype correlation of FBN1 was assessed, and the data showed that the patients with truncating and splicing mutations are more prone to developing severe aortic dissection than those with missense mutations, especially frameshift mutations (82.76% vs. 42.86%). In this study, 43 (20.28%) patients had a family history of sudden death or TAAD, whereas 132 (62.26%) did not (the remaining 37 were not available), and the positive rate of genetic testing was higher in TAAD patients with family history than in those without (76.74% vs. 18.94%). Conclusion: Our study concludes that genetic variation is an important consideration in the risk stratification of individualized prediction and disease diagnosis.

Automated summary

This study utilized NGS to screen 212 TAAD patients in northwestern China and found a 31.60% positive rate of (likely) pathogenic variants, with 77 variants first reported. A genotype-phenotype correlation of FBN1 was assessed, and it was observed that family history may affect the positive rate of genetic testing in TAAD patients.