转录因子GATA-4突变与先天性心脏病研究进展

先天性心脏病（CHD）是人类所有出生缺陷中最常见的疾病之一，调控心脏发育的基因发生突变会导致CHD，寻找CHD相关基因成为心血管领域研究焦点。锌指转录因子GATA-4是心脏前体细胞的最早期标志之一，是心脏发育过程中重要转录因子，该基因突变导致基因产物的转录活性下降，并影响其他心脏发育相关因子发挥作用，从而影响心脏发育。导致CHD。综述GATA-4结构特征、在心脏发育中的作用及其突变与CHD的关系。     

先天性心脏病相关转录因子Csx/Nkx2.5基因的研究

先天性心脏病(CHD)是常见的危害儿童健康的先天性疾病.调控心脏发育基因突变是CHD常见原因,同源盒基因Csx/Nkx2.5是心脏发育过程中最早表达的转录因子,该基因突变影响心脏发育,导致CHD.检测Csx/Nkx2.5基因突变可作为产前CHD诊断的一项指标.     

转录因子GATA-4突变与先天性心脏病研究进展

先天性心脏病(CHD)是人类所有出生缺陷中最常见的疾病之一,调控心脏发育的基因发生突变会导致CHD,寻找CHD相关基因成为心血管领域研究焦点.锌指转录因子GATA-4是心脏前体细胞的最早期标志之一,是心脏发育过程中重要转录因子,该基因突变导致基因产物的转录活性下降,并影响其他心脏发育相关因子发挥作用,从而影响心脏发育,导致CHD.GATA-4结构特征、在心脏发育中的作用及其突变与CHD的关系.     

胎儿先天性心脏病的孕期筛查

胎儿先天性心脏病 (简称先心病 )是严重影响围生儿结局的重要原因之一。目前我国每年约有 10余万先心病患儿出生 ,据统计 ,世界上活产婴儿中先心病的发病率为8‰[1] 。近年来 ,随着胎儿超声心动图的开展 ,胎儿先心病的产前诊断已取得了突破性进展 ,先心病的发生率已居新生儿畸形的首位 ,为及早诊断先心病 ,应采用经济、简便、无创伤及安全的超声筛查法 ,以便采取相应措施。1　胎儿先心病的孕期筛查方法　　虽然胎儿先心病的种类繁多 ,但多数先心病表现为四腔心不对称 ,常规的二维超声检查胎儿四腔心方法简便 ,重复性好 ,无创伤并易掌握 ,可…     

胎儿超声心动图筛查胎儿先天性心脏病的临床应用

为评价胎儿超声心动冈筛查胎儿心脏病的有效性，探讨其临床应用价值，进行了本研究。     

西藏林芝地区胎儿先天性心脏病的危险因素分析

目的:探究西藏林芝地区先天性心脏病(CHD)的发生情况及其相关危险因素的关系。方法:选择于2016年6月至2018年6月在林芝市人民医院产前检查和(或)分娩且为当地常住人口的2126例孕妇,孕中期常规进行胎儿CHD筛查及孕期危险因素的调查。经胎儿超声心动图诊断出胎儿心脏畸形病例纳入CHD组,将胎儿超声心动图检查结果正常的孕妇纳入对照组,所有胎儿出生后进一步检查以明确诊断。结果:CHD组纳入26例,产后均确诊为CHD;对照组纳入2100例,产后进行一般体检未见异常,心脏听诊未闻及杂音;CHD产前检出率1.22%。单因素分析结果显示,两组孕妇年龄、孕前体质量指数(BMI)、孕产史、孕前6个月至此次产前检查期间主动及被动吸烟史、孕早期补充叶酸及微量元素、孕期发热史及感染性疾病史、妊娠期合并糖尿病史比较,差异有统计学意义(P0.05)。多因素分析结果显示,孕前超重(OR=13.60,95%CI 5.04～36.66)及孕前肥胖(OR=67.33,95%CI 16.03～282.78)、孕前6个月至此次产前检查期间主动与被动吸烟史(OR=4.02,95%CI 1.59～10.17)、孕期发热史(OR=10.31,95%CI 1.56～68.29)、妊娠合并糖尿病史(OR=15.88,95%CI 3.90～64.63)是胎儿发生CHD的危险因素。结论:为降低先心病的发病及改善预后,应加强林芝地区孕妇的孕期保健知识宣教及孕期管理,及时进行有效产前检查。     

先天性心脏病的基因研究

先天性心脏病(congenital heart diseas,CHD)是由于心脏、血管在胚胎发育过程中发生障碍并导致心脏、血管在形态、结构、功能和代谢异常所致的一大类疾病,其发病率接近1%,居出生缺陷首位,严重危害胎儿、新生儿、婴幼儿及儿童健康.上世纪70年代前,少于30%的CHD患儿能存活到成年,如今随着外科和介入手术的发展,85%以上CHD患者至少能存活至16岁,并且大多数患者可以成功孕育下一代,但是其后代有着患CHD的高风险性.     

先天性心脏病相关转录因子Csx／Nkx2．5基因的研究

先天性心脏病(CHD)是常见的危害儿童健康的先天性疾病。调控心脏发育基因突变是CHD常见原因，同源盒基因Csx／Nkx2．5是心脏发育过程中最早表达的转录因子，该基因突变影响心脏发育，导致CHD。检测Csx／Nkx2．5基因突变可作为产前CHD诊断的一项指标。     

胎儿先天性心脏病151例围生结局及预后分析

目的:探讨各种胎儿先天性心脏病(简称先心病)的围生儿结局和预后,为产前咨询、产后处理提供证据.方法:回顾性分析2005年1月至2009年12月在广东省人民医院产前和(或)产后经彩色超声心动图检查诊断为胎儿先心病151例的临床资料,并分析随访至出生后1～5年的情况.结果:我院的胎儿先心病的发生率为1.25％(151/12056),其中活产104例,引产45例(包括死胎引产1例),死产2例;存活95例,死亡9例(自然死亡6例,心脏矫形术后死亡3例).简单型先心病占41.06％ (62/151),其中61.29％( 38/62)是产后诊断,存活率91.94％(57/62).复杂型先心病占58.94％ (89/151),＜28孕周诊断者占42.70％( 38/89),复杂型先心病的引产率46.07％(41/89),存活率42.70％(38/89).产前诊断的98例胎儿先心病仅有67例产前行胎儿染色体核型分析,染色体异常发生率为16.42％( 11/67).151例胎儿先心病共有25例患儿行心脏矫形手术治疗,其中简单型先心病8例(术后均存活),复杂型先心病17例(术后死亡3例).结论:简单型先心病可出生后观察、随访,预后好;近一半复杂型先心病可以在28周内明确诊断,某些复杂畸形可以经医患双方充分沟通后,决定是否引产或出生后限期手术;应重视对胎儿先心痛的染色体异常进行产前诊断.     

TBX1基因多态性与先天性心脏病的相关性

目的探讨TBX1基因多态性与先天性心脏病(先心病)的相关关系。 方法选择2004-10—2005-03在哈尔滨医科大学附属第二医院住院的先心病患儿99例，对照组96名(与先心病患儿年龄相近的健康儿童)。应用小剂量DNA提取技术及采用ABI Prism SNaPshot方法,检测了先心病患儿和对照组儿童的TBX1基因多态性。 结果经χ2检验，TBX1基因各基因型频率在对照组、先心病组之间均无显著性差异(P>005)；各等位基因频率在两组人群中差异均无显著性意义(P>005)。 结论未发现TBX1基因多态性与先天性心脏病之间存在相关关系。     

妊娠合并先天性心脏病的综合管理

医学进步使得更多先天性心脏病妇女可以生存至生育期年龄。妊娠后母体和胎儿并发症风险都会增加,心脏功能也会进一步损害。风险取决于先天性心脏病类型、血流动力学受损程度及并发症情况。加强对此类患者的综合管理,进行仔细的个体化、多学科的风险评估,制定详细的妊娠期随访、分娩和产后治疗计划可降低风险,改善围产结局,对降低孕产妇病死率具有重要的意义。     

年轻子宫内膜癌患者保留生育能力治疗的思考

最新发布的《CA CANCER J CLIN》报道称,2019年美国有70余万例子宫内膜癌患者,有超过5万的新发病例。子宫内膜癌已成为美国发病率排名第二的妇科肿瘤,仅次于乳腺癌［1］。随着经济及生活水平的提高,以及生育年龄延迟,我国子宫内膜癌的发病率越来越接近发达国家。据最新一期国家癌症中心数据,我国2015年子宫内膜癌新发病例居我国恶性肿瘤发病前10位,占女性全部恶性肿瘤发病的3.88%,这一数据也较2014年的3.79%有所上升。城市地区的子宫内膜癌发病率为11.35/10万,高于农村地区;在上海,子宫内膜癌新发病例已超过子宫颈癌［2］。 浏览更多请关注本刊微信公众号及当期杂志。     

FISH技术在先天畸形胎儿基因诊断中的应用探讨

目的应用荧光原位杂交技术（FISH）研究先天畸形胎儿中先心病相关基因的表达缺失率。方法选取在北京大学人民医院产前诊断为胎儿先天畸形病例31例，其中心血管畸形16例，非心血管畸形15例。产前经脐带血穿刺留取胎儿血。选取同期正常新生儿12例作为对照组，分娩时留取脐血。应用间期FISH方法，检测畸形胎儿及正常新生儿的TUPLE1基因表达缺失率。结果正常新生儿组与先天畸形胎儿组TUPLE1基因表达缺失率分别为0％和35．48％，两组相比较差异有显著性（P〈0．05）。心血管畸形与非心血管畸形胎儿组的TUPLE1基因表达缺失率分别为43．75％及26．67％，两组比较，差异无显著性（P〉0．05）。结论TUPLE1基因因素是胎儿先天性畸形的重要病因。     

ECMO and congenital heart disease

Although initially designed for respiratory failure, venoarterial extracorporeal membrane oxygenation (VA ECMO) has become a mainstay of therapy in the treatment of patients with congenital heart disease, providing preoperative and postoperative support for infants with temporary impairment of myocardial function. Postoperative support for pulmonary hypertension has allowed dramatic improvements in lesions such as total anomalous pulmonary venous connection. VA ECMO has also proven to be an acceptable bridge to cardiac transplantation in patients too small for currently available ventricular assist devices. Intraoperative elective use of ECMO has also provided a surgical environment with some specific advantages over conventional cardiopulmonary bypass for lesions such as long segment tracheal stenosis. The results of "rescue ECMO" or extracorporeal cardiopulmonary resuscitation (ECPR) has shown that many children with congenital heart disease are very salvageable despite sudden decompensation and arrest. These techniques of VA ECMO have evolved and improved over the last two decades, allowing expanded application of this life saving support.     

The Glu331del mutation in the CYP17A1 gene causes atypical congenital adrenal hyperplasia in a 46,XX female

17α-Hydroxylase deficiency is an uncommon type of congenital adrenal hyperplasia (CAH) caused by mutations in the CYP17A1 gene encoding both 17α-hydroxylase and 17,20-lyase, essential for sex steroids production. Main clinical features include lack of pubertal development, hypertension, and hypokalemia. We report the first case of a 46,XX female homozygote for the p.Glu331del mutation in the CYP17A1 gene showing an atypical clinical presentation. She was evaluated the first time for primary amenorrhea and delayed puberty in the presence of low levels of androgens, 17β-estradiol, serum cortisol, and high levels of progesterone and gonadotropins. After puberty, the patient did not show hypocortisolism and/or hypertension. She started estrogen therapy for pubertal induction, followed by ethinylestradiol/gestodene with clinical and biochemical stability during the follow-up period. At the age of 40 years, she developed hypokalemia and clinical signs of hypocortisolism. Oral corticosteroid treatment was started showing a prompt clinical improvement. Modeling analysis predicted the main outcome of the E331 deletion to impair cytochrome b5 binding, according to a major effect on the enzyme’s lyase activity. These data broaden the molecular and clinical spectrum of CAH caused by 17α-hydroxylase deficiency and adds to current genotype–phenotype correlations.     

Fetal congenital heart disease and intrauterine growth restriction: a retrospective cohort study

Objective: Fetal congenital heart disease may lead to abnormal fetal growth. Our objective was to estimate the association between fetal congenital heart disease (CHD) and intrauterine growth restriction (IUGR) in an effort to better inform clinical management of continuing pregnancies complicated by fetal congenital heart disease. Methods: In a retrospective cohort study, outcome data was collected from singleton pregnancies undergoing routine anatomic survey at a tertiary medical center between 1990 and 2008. Dedicated research nurses collected information on delivery outcomes in an on-going manner. Subjects with a prenatal diagnosis of fetal CHD were compared to those without CHD. Stratified analyses for isolated fetal CHD and major CHD were performed. The primary outcome was IUGR less than 10th percentile by the Alexander growth standard. Logistic regression was used to adjust for confounding variables and refine the estimates of risk. Results: Among 67,823 patients, there were 193 cases of fetal CHD (0.3%) and 5,669 cases of IUGR (8.4%). Prenatal diagnosis of CHD was associated with an increased risk of IUGR (23.8% vs. 8.5%, adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 2.4–4.6), and the risk was greatest in fetuses with major CHD (16.5% vs. 8.5%, aOR 2.1, 95% CI 1.3–3.2). Isolated CHD was also associated with an increased risk of IUGR (17.8% vs. 8.5%, aOR 2.2, 95% CI 1.4–3.7). Conclusion: Patients with a prenatal diagnosis of fetal CHD have a three-fold increase in risk of developing IUGR; patients with isolated fetal CHD are twice as likely to develop IUGR. Based on our findings, serial growth assessment may be a reasonable option for patients with fetal CHD diagnosed at routine anatomic survey.     

Csx/Nkx2.5基因在胚胎心脏的表达及在先天性心脏病中的突变检测

目的 了解Csx／Nkx 2．5基因在胚胎心脏发育过程中的表达情况及在先天性心脏病（先心病）患者中的突变情况。方法 采用免疫组化方法检测Csx／Nkx 2．5基因表达，采用PCR-SSCP-银染和DNA测序技术检测Csx／Nkx 2．5基因突变。结果Csx／Nkx 2．5基因在心房、小梁网中高表达。16周后心房表达趋于稳定，小梁网的表达稍有下降。在心室的表达早期较弱，逐渐升高，13至16周增加幅度最大，16周后表达趋于稳定。心外膜不表达。在126例先心病患儿、16例先心病胎儿和30例正常人中发现编码21位氨基酸密码子的第3位碱基的三种多态性：A、G、A／G。结论 Csx／Nkx 2．5基因在胚胎心脏发育过程中的表达有严格的时空规律，说明该基因在心脏发育过程中发挥重要作用。本研究中，无论是散发性或家族性先心病病例，均未检测到与先心病有关的突变。     

Neonatal hyperbilirubinemia and G71R mutation of the UGT1A1 gene in Turkish patients

Objective.?Nonphysiologic hyperbilirubinemia of unexplained cause is prevalent among Turkish newborns, suggesting that there might be genetic risk factors in this population. Mutation of the UGT1A1 gene, glycine to arginine at codon 71 (G71R), is related to the development of neonatal jaundice in East Asian populations but the frequency of this mutation is rare among Caucasian populations. There are insufficient data on the G71R mutation in Turkish newborns with hyperbilirubinemia. The aim of this study was to investigate the genotypic distribution of the G71R mutation and its relationship with nonphysiologic hyperbilirubinemia of unexplained cause in Turkish newborns.

Methods.?Polymerase chain reaction, restriction fragment length polymorphism and agarose gel electrophoresis techniques were used for detection of G71R mutation in 109 newborn infants: 39 with hyperbilirubinemia and 70 without hyperbilirubinemia.

Results.?The genotypic distribution for the mutation was 70 G/G, 32 A/G, 7 A/A genotypes and the mutated allele frequency was 0.22. The frequency of G71R mutation was 33.3 % (n?=?13) A/G, 7.7% (n?=?3) A/A in the hyperbilirubinemia group and 27.1% (n?=?19) A/R, 5% (n?=?4) A/A in the nonhyperbilirubinemia group. The difference between the groups was not statistically significant.

Conclusions.?Our results suggest that G71R mutation of UGT1A1 is not rare; however, an association between G71R mutation and hyperbilirubinemia of unexplained cause has not been shown in Turkish newborns.     

TIMP-1基因突变与卵巢恶性肿瘤临床病理关系的初步探讨

目的:探讨TIMP-1突变与临床的相关性。方法:采用PCR-SSCP染色技术和核苷酸序列测定对正常组织、良性卵巢肿瘤组织及恶性卵巢肿瘤组织中TIMP-1基因突变进行检测,并分析TIMP-1基因突变与其临床病理因素的关系。结果:(1)所有的标本TIMP-1第1,2,3编码外显子扩增产物均为一个带型,DNA测序显示未见突变;(2)TIMP-1基因第4外显子在恶性肿瘤组织中突变率为69.2%(27/39),高于良性肿瘤[20%(2/10)]和正常组织的[27.8%(5/18)],差异均有统计学意义(P=0.014,P=0.030);TIMP-1基因第5外显子在恶性肿瘤组织中突变率为61.5%(24/39),显著高于正常组织[22.2%(4/18)](P=0.013),但与良性肿瘤组织[40%(4/10)]比较无统计学差异(P=0.384)。9例(23.1%)编码外显子错译突变全部为卵巢恶性肿瘤。结论:卵巢恶性肿瘤组织中存在TIMP-1编码子突变现象,MMPs和TIMPs之间平衡失调可能与TIMP-1编码子突变有关。