Analysis of Genetic Contribution to Thoracic Aortic Aneurysm or Dissection in a Prospective Cohort of Familial and Sporadic Cases in East China

Background. Thoracic aortic aneurysm or dissection (TAAD) is a group of life-threatening diseases. Genetic etiology lead to some special characteristics on age of onset, clinical phenotype, and timing of intervention. Herein, we initiated a prospective trial to determine the prevalence of pathogenic variants in TAAD patients and to elucidate the traits related to harboring pathogenic variants. One hundred and one unrelated TAAD patients were sequenced and analyzed for 23 TAAD associated genes using a targeted PCR and next generation sequencing-based panel. Results. A total of 47 variants were identified in 52 TAAD patients (51.5%) including 6 pathogenic, 1 likely pathogenic and 40 variants of uncertain significance. The pathogenic or likely pathogenic (P/LP) variants in 4 disease-causing genes were carried by 1 familial and 6 sporadic cases (6.9%). Besides one familial TAAD, the FBN1 gene also harbored more than half of the P/LP variants in sporadic ones. The individuals with the age of onset less than 50 years and normotension massively increased the genetic risk. Conclusions. The TAAD cases with younger age at diagnosis and normotension were more likely to carry a P/LP variant, thus routine genetic testing will be beneficial to better prognosis through a genetically personalized care prior to acute rupture or dissection.