T-box 转录因子TBX20与心脏发育及人类先天性心脏病的研究进展

近年来,动物研究发现T-box基因家族的一个新成员Tbox20基因在心脏发育过程中起着重要作用.心脏发育与先天性心脏病之间有明显的相关性,提示TBX20基因在人类先天性心脏病的发生过程中可能起着重要作用.但目前关于TBX20基因与人类先天性心脏病相关性的研究甚少.该文综述了TBX20基因的结构、表达、在心脏发育中的功能与途径以及在人类先天性心脏病发生中的最新研究进展.     

转录因子家族与先天性心脏病关系的研究进展

先天性心脏病是一类最常见的出生缺陷病,主要由遗传因素和环境因素共同作用导致,是一种多基因遗传病,目前其发病机制尚不十分明确.心脏发育过程中有众多基因参与,而转录因子对心脏相关基因的表达起重要调控作用.该文系统阐述了GATA4/5/6、Nkx2.5、Nkx2.7、TBX1、TBX5和TBX20对心脏发育的影响以及转录因子间的相互联系,在分子水平上对先天性心脏病的发生有更深入的了解.     

转录因子TBX20与先天性心脏病发病机制研究进展

TBX20是T-box转录因子家族的一员,在心脏发育过程中发挥重要作用,在帮助维持成年人正常心功能方面也有一定作用。TBX20在心脏发育过程中既可作为转录激活因子也可作为转录抑制因子,并表现出复杂的时空调控作用。TBX20是先天性心脏病(congenital heart disease,CHD)的重要候选转录因子,其突...     

Tbx2基因调控胚胎心脏发育的研究进展

胚胎心脏的正常发育有赖于各相关基因的精确表达,涉及复杂的基因调控模式,其中任一环节出现偏差都会导致心脏畸形的发生.不同物种的Tbx2基因表达最终都局限在非腔室心肌区域的房室管,这提示Tbx2基因在心脏发育中时空表达的一致性和进化过程的高度保守性.Tbx2作为T-box转录因子家族的成员之一,主要参与心脏流出道和房室管的发生,通过调节下游目的基因的转录水平,从而引起一系列的调节通路变化.目前越来越多的研究表明,Tbx2表达水平或调控异常导致了不同模式动物心脏畸形的发生.临床报道也证实TBX2所在片段的微缺失/重复及其非编码区遗传变异与人类先天性心脏病的发生密切相关.该文综述了Tbx2在胚胎心脏发育中的功能、可能的调控机制及与先天性心脏病的关系.     

NKX2.5基因和TBX5基因在先天性心脏病试管婴儿中的突变检测

目的探讨患先天性心脏病的试管婴儿与自然受孕儿间是否存在NKX2.5基因和TBX5基因突变差异。方法应用聚合酶链反应结合DNA测序技术,对68例试管婴儿先天性心脏病患儿和98例自然受孕先天性心脏病患儿的NKX2.5基因编码区1、2和TBX5基因编码区4、5、8进行突变检测。结果在患先天性心脏病的试管婴儿与自然受孕儿中,均发现NKX2.5基因编码区1中第63位碱基发生突变(c.63AG),该位点基因型及等位基因频率的分布在两组间差异无统计学意义。NKX2.5基因编码区2和TBX5基因编码区4、5、8未检测到突变。结论先天性心脏病的试管婴儿与自然受孕儿间NKX2.5基因和TBX5基因突变无差异,推测辅助生殖技术并未引起NKX2.5基因和TBX5基因突变。     

转录因子在先天性房室隔缺损遗传学机制中的作用

先天性房室隔缺损是一种累及心脏房室瓣和房室间隔的先天性心脏病.心脏转录因子在心脏瓣膜发育及房室间隔的形成方面起重要作用,目前已知转录因子GATA4、NKX2.5、TBX5、ZIC3可能参与了房室隔缺损的发病机制,它们的表达异常或功能变化可能导致房室瓣膜及间隔的发育异常.     

转录因子在先天性房室隔缺损遗传学机制中的作用

先天性房室隔缺损是一种累及心脏房室瓣和房室间隔的先天性心脏病.心脏转录因子在心脏瓣膜发育及房室间隔的形成方面起重要作用,目前已知转录因子GATA4、NKX2.5、TBX5、ZIC3可能参与了房室隔缺损的发病机制,它们的表达异常或功能变化可能导致房室瓣膜及间隔的发育异常.     

心脏近端流出道隔心肌化过程及其机制

心脏锥干部畸形是常见的复杂性先天性心脏病.近年来发现"心肌化"过程是心脏近端流出道隔发育中的一个重要事件.调控心肌化的基因及相关分子机制的研究正在成为研究热点.了解这些机制在心肌化过程中的作用将有助于深入了解心脏流出道发育的涮控过程,对于进一步探讨产前的预防措施乃至开展基因治疗具有十分重要的意义.     

GATA6基因与先天性心脏病发病的关系

近期研究发现GATA6可能是先天性心脏病的一个致病候选基因,其编码产物GATA6转录因子是GATA转录因子家族中的一员,在心脏发育早期表达于胚胎中胚层,可以单独或与其他转录因子协同作用于心脏发育.近年对心脏流出道发育机制的研究发现,GATA6可以调控心脏神经嵴细胞向心脏流出道迁移.通过测序技术对GATA6外显子测序,找到多个非同义氨基酸突变(p.A178V、p.L198V、p.D404Y、p.E460X).这些突变会影响GATA6转录因子转录功能,并与先天性心脏病发病密切相关.在体内适当表达水平的GATA6对正常心脏发育是必须的,过表达的GATA6会引起胚胎心脏发育异常.GATA6转录因子可以与其他对心脏特异性转录因子相互作用,精密调控整个心脏发育过程.该文阐述GATA6基因与先天性心脏病发生关系的研究进展.     

法洛四联症相关易感基因的研究进展

先天性心脏病是胚胎发育过程中存在心血管结构或功能异常的一类疾病,是胎儿时期心血管系统发育异常、发育障碍或出生后未能退化所造成的心血管畸形,但其具体发病机制仍未阐明.法洛四联症是先天性心脏病中最严重的类型之一,包括室间隔缺损、主动脉骑跨、肺动脉狭窄和右心室肥厚.近年来的多项研究显示遗传因素参与了法洛四联症的发生,部分基因突变与法洛四联症的发生有很大关系,其中NKX2-5、GATA4、TBX5及TBX20已被证实与法洛四联症高度相关.该文主要围绕上述4个基因的研究进展,阐述法洛四联症的病因及发病机制.     

Circadian rhythm of heart rate and heart rate variability

BACKGROUND—Measurements of heart rate variability (HRV) are increasingly used as markers of cardiac autonomic activity.AIM—To examine circadian variation in heart rate and HRV in children.SUBJECTS—A total of 57 healthy infants and children, aged 2 months to 15 years, underwent ambulatory 24 hour Holter recording. Monitoring was also performed on five teenagers with diabetes mellitus and subclinical vagal neuropathy in order to identify the origin of the circadian variation in HRV.METHODS—The following variables were determined hourly: mean RR interval, four time domain (SDNN, SDNNi, rMSSD, and pNN50) and four frequency domain indices (very low, low and high frequency indices, low to high frequency ratio). A chronobiological analysis was made by cosinor method for each variable.RESULTS—A significant circadian variation in heart rate and HRV was present from late infancy or early childhood, characterised by a rise during sleep, except for the low to high frequency ratio that increased during daytime. The appearance of these circadian rhythms was associated with sleep maturation. Time of peak variability did not depend on age. Circadian variation was normal in patients with diabetes mellitus.CONCLUSION—We have identified a circadian rhythm of heart rate and HRV in infants and children. Our data confirm a progressive maturation of the autonomic nervous system and support the hypothesis that the organisation of sleep, associated with sympathetic withdrawal, is responsible for these rhythms.     

Circadian rhythm of heart rate and heart rate variability.

BACKGROUND: Measurements of heart rate variability (HRV) are increasingly used as markers of cardiac autonomic activity. AIM: To examine circadian variation in heart rate and HRV in children. SUBJECTS: A total of 57 healthy infants and children, aged 2 months to 15 years, underwent ambulatory 24 hour Holter recording. Monitoring was also performed on five teenagers with diabetes mellitus and subclinical vagal neuropathy in order to identify the origin of the circadian variation in HRV. METHODS: The following variables were determined hourly: mean RR interval, four time domain (SDNN, SDNNi, rMSSD, and pNN50) and four frequency domain indices (very low, low and high frequency indices, low to high frequency ratio). A chronobiological analysis was made by cosinor method for each variable. RESULTS: A significant circadian variation in heart rate and HRV was present from late infancy or early childhood, characterised by a rise during sleep, except for the low to high frequency ratio that increased during daytime. The appearance of these circadian rhythms was associated with sleep maturation. Time of peak variability did not depend on age. Circadian variation was normal in patients with diabetes mellitus. CONCLUSION: We have identified a circadian rhythm of heart rate and HRV in infants and children. Our data confirm a progressive maturation of the autonomic nervous system and support the hypothesis that the organisation of sleep, associated with sympathetic withdrawal, is responsible for these rhythms.     

胎儿心力衰竭

20世纪90年代以来,超声技术的发展使胎儿疾病宫内诊断成为可能.胎儿心力衰竭是许多胎儿疾病过程中的共同表现,常为多因素起源,而最后导致胎儿死亡的主要原因常是严重的心力衰竭.     

A heart with three arterial trunks (tritruncal heart)

Summary The case is described of a 4 ?-year-old girl with a previously unreported malformation: a heart with three arterial trunks, aorta, main pulmonary artery, and an intermediate vessel, called “intermediate trunk” because it was situated between the aorta and the main pulmonary artery. Each of these three arteries had a semilunar valve at its origin, and their lumens were completely separated from each other. The pulmonary trunk arose from the right ventricle, while the aorta and the intermediate trunk arose from the left ventricle. The intermediate trunk continued as the right pulmonary artery. The pulmonary trunk continued as the left pulmonary artery. The outflow tracts of both ventricles were normal. There were therefore three arterial trunks arising from a heart with two outflow tracts. Our hypothesis on the embryopathogenesis of this case is that there was double septation of the primitive arterial trunk and the aortic sac, without involvement of the conus. In addition, there was a malalignment between the truncal and conal septa. This entity, however rare, should be considered in the differential diagnosis of absent or anomalous right pulmonary artery. Supported by the Centro de Cooperación Iberoamericano, Madrid, Spain     

Successful orthotopic heart transplantation using a donor heart with ALCAPA

With the imbalance between donation rates and potential recipients growing, transplant programs are increasingly using non‐ideal organs from so‐called marginal donors. This is the first reported case of the intentional use of a donor heart with ALCAPA. The recipient was aged one yr with restrictive cardiomyopathy who had been supported with BiVAD for over six months. Function of the donor left ventricle was shown to be well preserved, with no obvious signs of ischemia, except for a fibrotic layer on the anterolateral papillary muscle of the mitral valve. To prevent coronary steal, the anomalous left coronary artery ostium from the MPA was oversewn prior to implantation. The transplanted heart spontaneously regained sinus rhythm immediately following cross‐clamp release and showed good contractility from the first postoperative echocardiogram. The patient continues to do well 18 months post‐transplant, with excellent function on echocardiography, and good flow on coronary angiography.