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P6499Genetic screening in 109 adult Chinese patients with thoracic aortic aneurysm and dissection


 
 
 Thoracic aortic aneurysm and dissection (TAAD) comprises a heterogenous group of cardiovascular urgencies, which could be further categorized into syndromic and non-syndromic entities. The accurate and timely identification of culprit genetic variants is of grave importance for TAAD patients, since different genetic defects have been associated with different risks for aortic dissection, thus different thresholds for preventive aortic intervention.
 
 
 
 With the advent of next-generation sequencing (NGS) techniques, accumulating records of rare variants have been found in TAAD patients, while inadequate functional validation also makes it difficult to give proper counsel for individual TAAD patients. Therefore, it is necessary for us to start re-evaluating clinical applications of genetic screening strategies in specific patient populations.
 
 
 
 From June 2016 to July 2017, genetic screening using an NGS-based panel of 18 candidate genes (FBN1, FBN2, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD3, COL1A1, COL3A1, COL5A2, COL5A1, PLOD1, ACTA2, MYH11, MYLK, PRKG1, MFAP5, and SKI) was applied in 109 adult TAAD patients from our institution. Patients with bicuspid aortic valve disease, complex congenital cardiac defect, aortic root infection, aortitis, pregnancy, and an age older than 70 years were excluded from the present study.
 
 
 
 Among 109 TAAD patients, 36 harboured an FBN1 variant, including 2 splicing site, 6 frame shift, 5 non-sense, and 23 mis-sense variants. The pathogenicity of mis-sense variants was further categorized into 10 disease-causing variants via database survey, 5 disease-causing variants via family survey, and 8 variants of uncertain significance (VUS). On the other hand, 25 patients harboured a non-FBN1 variant, including 3 established pathogenic variants on TGFBR1, TGFB2, and ACTA2 genes, as well as 22 VUS. Patients with an FBN1 variant displayed younger age, lower rate of hypertension, higher rate of aortic root aneurysm, and more frequent mitral valve prolapse, while an extreme male predominance (24/25) was observed in patients with a non-FBN1 variant.
 
 
 
 In an adult Chinese TAAD cohort, disease-causing genetic variants were found in 28.4% (31/109) of patients, with FBN1 mutations still being the single leading cause of disease. The present study advocated a genetic screening strategy emphasizing the detection of FBN1 mutations in adult Chinese TAAD patients, and further studies should address the pathogenicity and clinical relevance of non-FBN1 VUS in TAAD patients.
