Gladstone研究所的研究人员发现，仅丧失TBX5基因的一个拷贝就足以扰乱心脏细胞DNA的三维结构，破坏心脏正常发育所需的基因表达1。这一发现揭示了先天性心脏病的一个关键分子机制，而先天性心脏病每年影响约100名新生儿中的1人1。
该研究表明，TBX5基因充当DNA的"建筑师"角色，引导分子马达cohesin形成DNA环路1。当失去一个基因拷贝时，会引发广泛的基因组组织变化，导致不同的心脏细胞对TBX5缺失产生各异的反应1。研究人员推测，这种细胞水平的差异可能解释了为什么相同的基因突变会在患者中引发不同类型的心脏缺陷，且这一机制可能适用于其他先天缺陷1。这项研究由Benoit Bruneau博士和Katie Pollard博士担任高级作者，已于2026年7月23日发表在《科学》杂志上1。
Researchers at Gladstone Institutes have discovered that the loss of a single copy of the TBX5 gene disrupts the three-dimensional structure of DNA in heart cells, interfering with gene expression essential for cardiac development.1 The study reveals that TBX5 functions as a molecular architect, guiding the cohesin molecular motor to form DNA loops necessary for proper heart formation.1 This finding may explain why identical genetic mutations can result in different heart defects and could have implications for understanding other congenital abnormalities.1
The research, led by senior authors Benoit Bruneau, PhD and Katie Pollard, PhD, demonstrates that losing even one copy of TBX5 triggers widespread changes in genomic organization across heart cells.1 Individual heart cells exhibit varying responses to TBX5 loss, suggesting a complex mechanism underlying the disease.1 The study was published in Science on July 23, 2026.1
Congenital heart disease affects approximately 1 in 100 babies born each year, making this research particularly significant for understanding the genetic basis of a common birth condition.1
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