先天性心脏病GATA4基因突变研究进展

GATA4基因突变在先天性心脏病患儿中较为常见.目前为止,已发现超过120个突变位点,其中在室间隔缺损、房室间隔缺损或法洛四联症患者中多见,但突变基因型与临床表型间的关系至今仍未阐明.该文总结了在人类先天性心脏病中已发表的GATA4基因突变位点,并绘制出功能性改变的基因突变图谱.     

多重连接依赖的探针扩增技术检测先天性心脏病患儿的22q11微缺失

目的 检测先天性心脏病患儿的22q11微缺失情况.方法 采用商品化的多重连接依赖探针扩增(Multiplex ligation dependent probe amplification,MLPA)P250试剂盒,检测100例散发的先天性心脏畸形样本,其中40例产前超声诊断为心脏畸形的胎儿,60例为先天性心脏病患儿.结果 心脏畸形的胎儿有2例为22q11微缺失,先天性心脏病患儿有1例22q11微缺失;3例检测出22q11微缺失的患儿,2例为3M典型缺失,1例为非典型缺失.结论 在先天性心脏病患儿中存在22q11微缺失.

Abstract：

Objective To detect 22q11 microdeletion in the children and fetuses affected by congenital heart defects.Method MLPA P250 kit was used to detect 22q1 1 microdeletion in 100 cases of sporadic congenital heart defects including 40 fetuses and 60 patients diagnosed by ultrasound.Result Two cases from the fetuses and 4 case from the patients were found to have 22q11 microdeletion.Conclusion Three cases had 22q11 microdeletion in the congenital heart defects.     

MRI技术在胎儿先天性心脏病诊断中的应用

先天性心脏病是造成新生儿死亡的主要原因之一.在产前对胎儿先天性心脏病进行诊断、评估预后是目前围生医学发展的重要内容.胎儿心脏彩超对于孕中期胎儿先天性心脏病的诊断具有相对较高的灵敏度,是胎儿先天性心脏畸形诊断的金标准.胎儿心脏核磁共振技术在过去十年内发展迅速,其视野大、可重复性好等优点在某些情况下可以弥补胎儿心脏超声的不足,但其技术上的问题也局限了其在临床上的应用,目前被认为是胎儿先天性心脏病的二线诊断方法.该文就胎儿心脏核磁共振技术在胎儿先天性心脏病诊断中应用的方法、优势以及局限性进行综述.     

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.     

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.     

三房心1例

三房心是一种罕见的先天性心脏病,约占先天性心脏畸形的0.1%,我院近期收治1例,疗效较好,现报告如下。     

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.     

先天性心脏病单基因突变研究进展

目前已日益明确许多以往认为多因子病因学的心脏缺损与单基因突变有关.该文综述了部分遗传综合征和非综合征先天性心脏病的单基因突变研究进展及基因型-心脏表型之间的相关性.对先天性心脏病遗传基础的认识有助于指导诊断、判断预后、进行遗传咨询和系谱分析,并有望通过基因工程进行心肌再生或细胞移植从而达到最终修复心脏缺损的目的.     

常伴先天性心脏病的人类综合征研究进展

先天性心脏病是一种常见的先天畸形,有时与一些心外畸形并存表现为某种可识别的综合征。该文就常伴心脏畸形的Alagille综合征、CHARGE综合征、DiGeorge综合征、Holt-Oram综合征、Noonan综合征及Ritscher-Schinzel综合征作一综述,通过了解这些综合征的临床特点、常见心脏畸形的类型、分子遗传学及相关候选基因的研究进展,有助于临床全面正确的诊断,同时为进一步阐明先天性心脏病分子发病机制提供重要线索。     

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。     

RECENT ADVANCES IN THE UNDERSTANDING OF GENETIC CAUSES OF CONGENITAL HEART DEFECTS

The clinical approach to children with congenital heart defects (CHD) has been revolutionized during the past four decades by developments in diagnostics and therapeutics. In contrast, a profound understanding of the causes of the majority of CHD has only begun to emerge within the past few years. Prior epidemiological studies suggested that Mendelian disorders constituted a very small percentage of CHD and that polygenic inheritance was responsible for the majority of cases. Recent discoveries, largely achieved with molecular genetic studies, have provided new insights into the genetic basis of heart malformations. These studies have shown that CHD caused by single gene or single locus defects is more common than had been suspected. In addition, a higher percentage of heart malformations occur in the context of familial disease than was evident previously. In this review, molecular genetic studies of specific heart lesions and syndromes with CHD are reviewed. Progress on the Human Genome Project has accelerated identi cation of genes for Mendelian traits with heart defects, and it is anticipated that disease genes for most single gene traits will be known within a few years. Future challenges include utilizing this emerging genetic information to improve diagnosis and treatment of children with CHD, and harnessing the power of genomics to analyze isolated heart defects with complex inheritance patterns.     

Outcome of prenatally diagnosed congenital heart disease: an update

The objective of this study was to compare the outcome of prenatally diagnosed congenital heart disease (CHD) in a recent time period with previously reported experience. All cases of fetal CHD during the time period 1993 to 1999 were analyzed in terms of their outcome. During this time frame, 408 cases of fetal CHD were detected. Of these, 84% of mothers were referred because of suspicion of a cardiac anomaly during an obstetric scan. The mean gestational age at diagnosis was 26 weeks. Termination of pregnancy occurred in 98 cases. There were 92 deaths in the continuing pregnancies and a survival rate of 60%. The detection rate of CHD prenatally continues to increase as obstetric screening for cardiac malformations becomes more widespread. Diagnostic categories continue to be skewed toward more complex forms of malformation, although comparisons with previous studies show some trends. In particular, there are proportionately fewer pregnancies with extracardiac malformations. In addition, the outcome in continuing pregnancies is substantially improved from previous reports.     

Risk factors in congenital heart disease

A case-control study was conducted to investigate the risk factors of congenital heart disease (CHD). The cases were 346 children with CHD who were admitted to a university hospital in Tehran from 1995 to 2000 and controls (n=346) were randomly selected from children without CHD who were admitted during the same period. The medical records of both cases and controls were reviewed. Ten risk factors were studied and found to be more prevalent among cases (47%) than controls (35%, p < 0.005). Extracardiac malformations (OR, 31.1; CI95, 15.9-60.9; p < 0.001) and chromosomal abnormalities (OR, 34.05; CI95, 23.3-49.8; p < 0.001) were significant risk factors for CHD. Dysmorphic syndromes (p < 0.05) and CHD in siblings (p < 0.001) were also significant risk factors. Maternal illness and drug use in the first trimester of pregnancy, maternal history of previous abortions and stillbirths, parental consanguinity, and parental cardiac lesions were not significant risk factors for CHD in offspring. Results suggest that genetic factors more than environmental or reproductive factors can increase the occurrence of cardiac defects.     

Proportion of malformations and genetic disorders among cases encountered at a high-care unit in a children’s hospital

Genetic disorders and birth defects account for a high percentage of the admissions in children’s hospitals. Congenital malformations and chromosomal abnormalities are the most common causes of infant mortality. So their effects pose serious problems for perinatal health care in Japan, where the infant mortality is very low. This paper describes the reasons for admissions and hospitalization at the high-care unit (HCU) of a major tertiary children’s referral center in Japan. We retrospectively reviewed 900 admission charts for the period 2007–2008 and found that genetic disorders and malformations accounted for a significant proportion of the cases requiring admission to the HCU. Further, the rate of recurrent admission was higher for patients with genetic disorders and malformations than for those with acquired, non-genetic conditions. Over the past 30 years, admissions attributed to genetic disorders and malformations has consistently impacted on children’s hospital and patients with genetic disorders and malformations form a large part of this facility. These results reflect improvements in medical care for patients with genetic disorders and malformations and further highlight the large proportion of cases with genetic disorders, for which highly specialized management is required. Moreover, this study emphasizes the need for involvement of clinical geneticists in HCUs at children’s hospitals.     

Update in Adult Congenital Cardiac Surgery

The number of grown-up patients with congenital heart disease (GUCH) is constantly increasing and will equal the number of children requiring surgery for congenital heart disease (CHD). Specialized centers dealing with the medical and paramedical problems of these patients are required. GUCH patients can be divided into the following groups: (1) patients with minor cardiac malformations presenting at adult age for first treatment; (2) patients presenting for correction as adults because they are either naturally balanced or were surgically palliated; (3) patients presenting for expected reoperations after correction in childhood; (4) patients requiring repair of residual defects after correction; (5) patients developing heart failure after correction or palliation of CHD requiring thoracic transplantation; and (6) patients developing acquired heart disease in addition to CHD. Special aspects of malformations frequently occurring in GUCH patients are discussed in detail. Acquired heart disease in this patient population is expected to increase in the coming decades as survivors of CHD grow old.     

Usefulness of Fetal Three-Dimensional Ultrasonography for Detecting of Congenital Heart Defects and Associated Syndromes

Congenital heart defects (CHDs) occur in 1% of live-born infants and frequently are associated with extracardiac malformations. This study aimed to assess the feasibility and accuracy of three-dimensional ultrasonography (3DUS) in fetuses with CHD and to investigate whether 3DUS can add information about the heart and general fetal morphology that shows other congenital malformations or suggests syndromes. For 30 fetuses affected by CHD, 3DUS was performed using a Sonos 7500 ultrasound machine with a cardiac 3D transducer. In 44% of the exams, 3DUS was completely diagnostic for the CHD, providing additional information in 28% of the exams. Furthermore, 3DUS showed 82% of associated malformations, providing the complete diagnosis in 57% of the cases and helping with recognition of syndromes in others. The diagnostic accuracy of 3DUS was superior, with a higher number of acquisitions per exam. Performance was better in fetuses younger than 24 weeks for general morphologic details and in fetuses older than 24 weeks for the heart morphology.     

先天性心脏病伴神经发育障碍的临床表现及遗传学研究进展

近年来研究发现先天性心脏病(CHD)患儿伴神经发育障碍(NDDs)的风险正逐年增加,包括认知、适应性、运动、语言、孤独症谱系障碍等。已通过结构及功能神经成像等影像学检查证实CHD患儿大脑发育存在异常,可能为宫内发育不良所致。拷贝数变异(CNVs)等基因异常对CHD伴NDDs具有重要影响。一些参与载脂蛋白E产生、Wnt信号传导通路和组蛋白修饰的基因变异以及1q21.1、16p13.1-11和8p23.1遗传位点变异均与CHD和NDDs相关。了解其中的相互联系对CHD患者的风险分层、疾病分类、筛查及药物治疗具有重要意义。     

围孕期营养因素与先天性心脏病发病的关系

先天性心脏病是人体在胚胎发育时期受各种因素影响导致心脏及血管发育异常的先天性畸形.先天性心脏病是人类最常见的先天畸形,是导致婴儿发病和病死的重要原因.即使可以经过外科手术矫治畸形,先天性心脏病患儿也要面临各种手术并发症甚至疾病复发的风险,给社会带来巨大的经济压力.目前普遍认为先天性心脏病的发生受遗传因素和环境因素的共同影响.近年来围孕期营养因素与先天性心脏病的发病关系成为研究热点.研究结果显示,叶酸及其他围孕期营养素与先天性心脏病的发生有密切关系,围孕期母亲适当补充这些营养素可降低子代先天性心脏病的发生风险.该文就叶酸、维生素A、锌、维生素B、维生素E围孕期关键营养因素与先天性心脏病的关系,从病因、发病机制及预防方面进行综述,为疾病的预防提供基础.     

The evolution of diagnostic trends in congenital heart disease: A population-based study

OBJECTIVE: To analyse historical trends in diagnosis of congenital heart disease (CHD) in all diagnosed cardiac malformations born between 1945 and 1994 in a population-based study, the first of its type. METHODOLOGY: Retrospective analysis of age and mode of diagnosis was carried out in 953 patients with CHD, in the setting of a regional hospital providing diagnostic and follow up services for all of Malta. Main outcome measures were age at diagnosis, cumulative percentage diagnosis by age and mode of diagnosis. RESULTS: A significant negative correlation of age at diagnosis with time was found for both lesions not requiring intervention, and requiring intervention (P < 0.0001). Cumulative percentage diagnosis by age increased progressively with time. Echocardiography increased the birth prevalence of definitively diagnosed defects, particularly of lesions not requiring intervention. The annual number of cardiac catheters for these conditions has decreased with an increased number and proportion of interventional catheters. The current catheterization rate for CHD is 6.1/100 000 population. CONCLUSION: Echocardiography has led to an increase in the diagnosis in the birth prevalence of CHD, and provided early diagnosis, supplanting cardiac catheterization as a primary diagnostic tool.