TBX5 pathogenic variant in a patient with congenital heart defect and tracheal stenosis

IF 1.3 4区 医学 Q3 PEDIATRICS
Kaori Yamoto, Fumiko Kato, Masaya Yamoto, Koji Fukumoto, Kenji Shimizu, Hirotomo Saitsu, Tsutomu Ogata
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引用次数: 0

Abstract

Congenital tracheal stenosis is a rare life-threatening disorder caused by narrow O-shaped tracheal ring without smooth muscle. Its underlying genetic cause has not been elucidated. We performed whole exome sequencing in a patient with congenital tracheal stenosis and congenital heart defect, and identified a de novo pathogenic TBX5 variant (NM_181486.4:c.680T>C, p.(Ile227Thr)). The Ile227Thr-TBX5 protein was predicted to have a decreased stability by in silico protein structural analyses, and was shown to have a significantly reduced activity for the NPPA promoter by luciferase assay. The results, together with the expression of mouse Tbx5 in the lung and trachea and the development of tracheal cartilage dysplasia in the lung-specific Tbx5 null mice, imply the relevance of TBX5 pathogenic variants to congenital tracheal stenosis.

一名先天性心脏缺陷和气管狭窄患者的 TBX5 致病变体
先天性气管狭窄是一种罕见的危及生命的疾病,由没有平滑肌的 O 形狭窄气管环引起。其潜在的遗传原因尚未阐明。我们对一名患有先天性气管狭窄和先天性心脏缺陷的患者进行了全外显子测序,发现了一个新的致病性 TBX5 变体(NM_181486.4:c.680T>C, p.(Ile227Thr))。硅学蛋白结构分析预测 Ile227Thr-TBX5 蛋白的稳定性会降低,荧光素酶分析表明 Ile227Thr-TBX5 蛋白对 NPPA 启动子的活性显著降低。这些结果以及小鼠 Tbx5 在肺和气管中的表达和肺特异性 Tbx5 空腹小鼠气管软骨发育不良的发生,都意味着 TBX5 致病变体与先天性气管狭窄有关。
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来源期刊
Congenital Anomalies
Congenital Anomalies PEDIATRICS-
自引率
0.00%
发文量
49
审稿时长
>12 weeks
期刊介绍: Congenital Anomalies is the official English language journal of the Japanese Teratology Society, and publishes original articles in laboratory as well as clinical research in all areas of abnormal development and related fields, from all over the world. Although contributions by members of the teratology societies affiliated with The International Federation of Teratology Societies are given priority, contributions from non-members are welcomed.
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