Differential Analysis of Pathogenic Variants in Thoracic Aortic Aneurysm and Dissection at Different Ages.

Objective

To identify genetic variants associated with Stanford A thoracic aortic aneurysm and dissection (ATAAD) using whole-exome sequencing (WES) and analyze positive mutation rates among patients of different onset ages.

Methods

WES was performed on 62 sporadic Chinese ATAAD patients (51-74 years old), and then grouped based on onset age together with 73 previously reported TAAD patients (19-50 years old): ≤35, 36-45, 46-55, and >55 years. The proportion of patients with pathogenic/likely pathogenic (P/LP) variants in TAAD causal genes was compared across groups.

Results

The average onset age of the 62 patients was 57.66 years. Eight P/LP variants were identified (two novel, six previously described) in five known TAAD causal genes (FBN1, SMAD3, TGFBR2, TGFB2, and MYLK) in eight individuals. P/LP variant positive rates among patients across age groups were: 22.73% for ≤35 years, 32% for 36-45 years, 15.52% for 46-55 years, and 3.33% for >55 years. Significant differences (p = 0.0077) were observed between 36-45 and >55 years group.

Conclusions

ATAAD patients aged 36-45 years old at diagnosis had a higher chance of having a P/LP variant and patients >55 years old had the lowest P/LP diagnostic rate. Therefore, gene screening in ATAAD patients ≤55 years old is key to improved diagnostic rate.