Case report: Novel TBX5-related pathogenic mechanism of Holt–Oram syndrome

Frontiers in Genetics

Genetics

Chengxiu Zhao¹  Yue Zheng²  Tong Li²  Yuheng Lang²  Bingcai Qi³  Gang Wang³  Weifeng Zheng³  Hu Zhai³  Zhiqiang Luo³ 

[1] Department of Anesthesiology, Handan First Hospital, Handan, China;Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China;School of Medicine, Nankai University, Tianjin, China;Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China;Artificial Cell Engineering Technology Research Center, Tianjin, China;Tianjin Institute of Hepatobiliary Disease, Tianjin, China;Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China;Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China;Artificial Cell Engineering Technology Research Center, Tianjin, China;Tianjin Institute of Hepatobiliary Disease, Tianjin, China;

关键词: Holt–Oram syndrome;    Tbx5;    ChIP;    case report;    SNP;   

DOI  :  10.3389/fgene.2023.1063202

 received in 2022-10-06, accepted in 2023-02-10,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Holt–Oram syndrome (HOS) is a rare genetic disorder characterized by upper limb abnormalities, congenital heart defects, and/or conduction abnormalities. Sequence alteration of T-box transcription factor 5 (TBX5) is correlated with the incidence of HOS.Case description: We present the case of a 24-year-old female with upper limb alterations (congenital dysplasia in the wrist and elbow joints) and an anomalous left main trunk arising from the right coronary sinus. The patient inherited a base T (reference C) at rs883079 from her mother and base C (reference T) at rs10850326 from her father, both of which belong to the 3′-untranslated region (UTR) of the TBX5 gene; no alterations in TBX5 expression or single-nucleotide polymorphisms (SNPs) in other exon areas were found. We explored the effects of TBX5 on cardiomyocytes using the HL-1 cell line and TBX5-knockdown cells.Discussion: Quantitative polymerase chain reaction analysis demonstrated that TEKT2, TEKT4, and SPTB expression decreased after TBX5 knockdown, while chromatin immunoprecipitation analysis further revealed that TBX5 binds to the TEKT2, TEKT4, and SPTB promoter regions to promote gene transcription. Our findings support a novel TBX5-related pathogenic mechanism in HOS.

【 授权许可】

Unknown   
Copyright © 2023 Lang, Zheng, Qi, Zheng, Zhao, Zhai, Wang, Luo and Li.