A systematic study of mosaicism in heritable thoracic aortic aneurysm and dissection

Hang Yang; Guoyan Zhu; Weizhen Zhou; Mingyao Luo; Yujing Zhang; Yinhui Zhang; Chang Shu; Zhou Zhou

doi:10.1016/j.ygeno.2021.12.002

A systematic study of mosaicism in heritable thoracic aortic aneurysm and dissection

Genomics. 2022 Jan;114(1):196-201. doi: 10.1016/j.ygeno.2021.12.002. Epub 2021 Dec 16.

Authors

Hang Yang¹, Guoyan Zhu¹, Weizhen Zhou¹, Mingyao Luo², Yujing Zhang¹, Yinhui Zhang¹, Chang Shu², Zhou Zhou³

Affiliations

¹ State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
² State Key Laboratory of Cardiovascular Disease, Center of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
³ State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Electronic address: zhouzhou@fuwaihospital.org.

PMID: 34921932
DOI: 10.1016/j.ygeno.2021.12.002

Abstract

Mosaicisms are often overlooked in routine molecular diagnosis. Although not common, they are of great significance for accurate diagnosis and genetic counseling. In this study, we systematically evaluated the frequency of mosaicisms in both asymptomatic parents and affected patients with thoracic aortic aneurysm and dissection (TAAD). Next-generation sequencing (NGS) data from 1085 patients was reanalyzed with a more lenient allele frequency to detect potential mosaic variants. In addition, parental mosaicisms were investigated in 80 TAAD families. Finally, a total of six mosaic variants were detected in our cohort. Three of them were identified in symptomatic patients and three were in asymptomatic parents. Notably, a low-level mosaic variant in TGFB2 was detected combined with a causative FBN1 variant in patient AD2001, which might partially explain the clinical heterogeneity in his family. Our study hinted that it is necessary and feasible to implement mosaicism analysis in routine molecular diagnosis.

Keywords: MFS; Mosaicism; Next-generation sequencing; TAAD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aortic Aneurysm, Thoracic* / diagnosis
Aortic Aneurysm, Thoracic* / genetics
Aortic Dissection* / diagnosis
Aortic Dissection* / genetics
High-Throughput Nucleotide Sequencing
Humans
Mosaicism
Mutation