Gene-phenotype correlation analysis of 226 cases of sporadic thoracic aortic diseases in southern China
10.3760/cma.j.cn112434-20210120-00020
- VernacularTitle:226例中国南方人群散发性主动脉疾病的基因-临床表型相关性分析
- Author:
Ying LI
1
;
Miaoxian FANG
;
Changjiang YU
;
Chuangwen ZHANG
;
Qiuji WANG
;
Jue YANG
;
Xin LI
;
Tucheng SUN
;
Ruixin FAN
Author Information
1. 广东省人民医院 广东省心血管病研究所 广东省医学科学院心外科，广州 510080
- Keywords:
Thoracic aortic dissection;
Thoracic aortic aneurysm;
Gene mutation;
Phenotype
- From:
Chinese Journal of Thoracic and Cardiovascular Surgery
2022;38(6):348-356
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To identify the causative genes of sporadic thoracic aortic aneurysm or dissection (TAAD) and their correlation with clinical phenotype in the southern Chinese.Methods:We analyzed 11 core genes of TAAD probands without specific family history of 226 cases by next-generation sequencing technology, and performed sanger sequencing for their close relatives. Clinical data of each patient, including age of onset, syndromic phenotypes, involvement of aortic root, aortic maximum diameter and D-dimer were collected. And statistical software SPSS was used to evaluate the correlation between clinical phenotypes and gene mutations.Results:A total of 106 variants were detected in 226 probands with gene-positive frequency of 44.69%, consist of 16 pathogenic (P) variants, 18 likely pathogenic (LP) variants and 71 variants of uncertain significance (VUS). More than half of the mutations were from the non-syndromic TAAD, in which the FBN1 still was the most common causative gene. Earlier age of onset, an increase of women, larger diameter of aorta, Stanford B dissection and severe aortic regurgitation were likely to occur on carriers of P/LP, while thoracic aortic aneurysm occurs on carriers of VUS. Phenotype of both syndrome and dissection with aneurysm could increase the likelihood of carrying gene mutation, but D-dimer and involvement of aortic root couldn’t.Conclusion:Patients with sporadic aortic diseases in southern China have significant genetic heterogeneity and specific correlation between their clinical phenotype and gene mutation, especially in non-syndromic population. Earlier age of onset in carriers of FBN1 or ACTA2 genes, and larger maximum diameters of aorta in carrier of P/LP.
