Lang Yuheng, Zheng Yue, Qi Bingcai, Zheng Weifeng, Zhao Chengxiu, Zhai Hu, Wang Gang, Luo Zhiqiang, Li Tong
Department of Heart Center, Tianjin Third Central Hospital, Tianjin, China.
School of Medicine, Nankai University, Tianjin, China.
Front Genet. 2023 Mar 1;14:1063202. doi: 10.3389/fgene.2023.1063202. eCollection 2023.
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. 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. 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.
霍尔特-奥勒姆综合征（HOS）是一种罕见的遗传性疾病，其特征为上肢异常、先天性心脏缺陷和/或传导异常。T盒转录因子5（TBX5）的序列改变与HOS的发病率相关。我们报告了一例24岁女性病例，该患者存在上肢改变（腕关节和肘关节先天性发育异常）以及一条异常的左主干发自右冠状动脉窦。该患者从母亲那里遗传了rs883079位点的碱基T（参考碱基为C），从父亲那里遗传了rs10850326位点的碱基C（参考碱基为T），这两个位点均属于TBX5基因的3'非翻译区（UTR）；未发现TBX5表达有改变，其他外显子区域也未发现单核苷酸多态性（SNP）。我们使用HL-1细胞系和TBX5基因敲低细胞研究了TBX5对心肌细胞的影响。定量聚合酶链反应分析表明，TBX5基因敲低后，TEKT2、TEKT4和SPTB的表达降低，而染色质免疫沉淀分析进一步显示，TBX5与TEKT2、TEKT4和SPTB的启动子区域结合以促进基因转录。我们的研究结果支持了一种新的与HOS相关的TBX5致病机制。
