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1.
内脏异位是由于左右非对称性发育异常所致,常与胸腹腔器官的异常偏侧化有关。心脏经常受累,且心脏受累的严重程度通常决定其预后效果。内脏异位患者有特征性的心血管畸形、内脏器官的异常排列以及中线结构发育畸形。在内脏异位患者中第一个被发现有突变的基因是编码锌指转录因子的ZIC3。很多研究证实,ZIC3突变可导致X连锁内脏异位,而且在孤立性先心病中也发现了ZIC3的突变。至今,在内脏异位患者中发现有13个ZIC3突变,其中包括无义突变、错义突变、沉默突变、移码突变以及易位突变等。然而,ZIC3基因在内脏异位,特别是伴复杂先心病中的致病机理仍不是很清楚。本文就ZIC3结构、作用、突变以及其在内脏异位伴先心病中的研究现状及存在的问题做一综述。 相似文献
2.
Chhin B Hatayama M Bozon D Ogawa M Schön P Tohmonda T Sassolas F Aruga J Valard AG Chen SC Bouvagnet P 《Human mutation》2007,28(6):563-570
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The ZIC gene family in development and disease 总被引:17,自引:0,他引:17
4.
Petra Werner Prasuna Paluru Anisha M. Simpson Brande Latney Radhika Iyer Garrett M. Brodeur Elizabeth Goldmuntz 《Human mutation》2014,35(12):1459-1468
Congenital heart defects (CHDs) are the most common major birth defects and the leading cause of death from congenital malformations. The etiology remains largely unknown, though genetic variants clearly contribute. In a previous study, we identified a large copy‐number variant (CNV) that deleted 46 genes in a patient with a malalignment type ventricular septal defect (VSD). The CNV included the gene NTRK3 encoding neurotrophic tyrosine kinase receptor C (TrkC), which is essential for normal cardiogenesis in animal models. To evaluate the role of NTRK3 in human CHDs, we studied 467 patients with related heart defects for NTRK3 mutations. We identified four missense mutations in four patients with VSDs that were not found in ethnically matched controls and were predicted to be functionally deleterious. Functional analysis using neuroblastoma cell lines expressing mutant TrkC demonstrated that one of the mutations (c.278C>T, p.T93M) significantly reduced autophosphorylation of TrkC in response to ligand binding, subsequently decreasing phosphorylation of downstream target proteins. In addition, compared with wild type, three of the four cell lines expressing mutant TrkC showed altered cell growth in low‐serum conditions without supplemental neurotrophin 3. These findings suggest a novel pathophysiological mechanism involving NTRK3 in the development of VSDs. 相似文献
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6.
Thomas W. Sadler 《American journal of medical genetics. Part A》2015,167(11):2563-2565
7.
George C. Gabriel Cecilia W. Lo 《American journal of medical genetics. Part C, Seminars in medical genetics》2020,184(1):90-96
Congenital heart defect is one of the most common structural birth defects in the human population. It is highly associated with heterotaxy, a birth defect involving randomized left–right patterning of visceral organ situs. Large scale mouse forward genetics have led to the finding of a central role for cilia in CHD pathogenesis, with some cilia and non‐cilia mutations causing CHD with heterotaxy. Interestingly, many of the mutations causing CHD with heterotaxy can give rise to three laterality outcomes comprising normal situs solitus, mirror symmetric situs inversus totalis, or randomized situs with heterotaxy. Given CHD is largely observed only with heterotaxy, this suggests a new paradigm is needed for investigating the genetics of CHD associated with heterotaxy. Furthermore, analysis of data from multiple large birth cohorts have independently confirmed a broader involvement of laterality disturbance in CHD. This was demonstrated by the common cooccurrence of rare laterality defects with CHD lesions of a wide spectrum. These findings suggest left–right patterning is tightly intertwined with the developmental processes that regulate cardiac morphogenesis and its disturbance may contribute to all types of CHD even in the absence of laterality defects. 相似文献
8.
同种异体带瓣管道在小儿复杂先天性心脏病中的应用 总被引:2,自引:0,他引:2
目的 探讨同种异体带瓣管(VHC)在复杂先天性心脏病(先心病)中的临床应用价值。方法 1993年-2000年共应用VHC重建右心室流了道治疗各种复杂先心病9年。VHC均采用同种异体带瓣主动脉;术后常规监测心肺功能,呼吸机辅助呼吸,应用正性肌力药物和血管扩张剂等辅助心功能。结果 8例成活,1例死亡,死亡率11.1%,死亡原因急性右心衰竭,合并纵隔感染2例,经清创引流治愈。随访3-6年,患儿生长发育良好,能正常上学;无远期死亡。结论 VHC对某些复杂先心病有广泛的应用前景。 相似文献
9.
目的观察皮肤粘合剂“爱必肤“(EPIGLU,主要成分为2-乙基氰丙烯酸酯)应用于小儿先天性心脏病术后切口的效果.方法将“爱必肤“点涂于先天性心脏病后对合良好的皮肤切口表面共30例,并观察12天.结果29例切口愈合较好或仅有轻微开裂,1例有部分开裂(重新缝合后愈合).4例有伤口渗血,2例较多.所有例数均未见过敏反应,未见皮肤感染.结论皮肤粘合剂“爱必肤“粘合对合良好的皮肤切口效果确实可靠,不需拆线,组织反应小,有广泛的临床应用前景. 相似文献
10.
Karsdorp PA Kindt M Rietveld S Everaerd W Mulder BJ 《International journal of behavioral medicine》2008,15(3):232-240
Background: Previous studies have shown that patients with congenital heart disease (ConHD) report a diminished health-related quality
of life. Purpose: This study examines the mechanisms by which ConHD affects health-related quality of life. We hypothesize that (1) the relation
between trait anxiety and quality of life is mediated by a negative interpretation bias for heart sensations, specifically
in ConHD, and that (2) the relation between trait anxiety and interpretation bias is mediated by state anxiety. Method: Sixty-six patients with ConHD and 50 healthy participants read a vignette about a person experiencing ambiguous heart-related
sensations. Interpretation bias to these sensations was assessed with the Implicit Models of Illness Questionnaire. Participants
completed Spielberger trait and state anxiety questionnaires and the physical subscales of a quality-of-life questionnaire.
Results: Path-analysis demonstrated that interpretation bias mediated the relation between trait anxiety and daily functioning. However,
trait anxiety and interpretation bias were less influential with respect to gross motor functioning. Moreover, state anxiety
mediated the relation between trait anxiety and interpretation bias. Conclusion: These results suggest that patients with ConHD who display both elevated levels of trait and state anxiety exhibit the most
pronounced negative interpretation bias for heart sensations and in turn diminished daily functioning.
The authors gratefully acknowledge Conor Dolan and Jelte Wicherts for their statistical advice and Kiki Hohnen for her grammatical
advice. The report was written as part of a project funded by the Dutch Heart Foundation (99.038). 相似文献
11.
Behavioral Adjustment of Children with Surgically Palliated Complex Congenital Heart Disease 总被引:7,自引:2,他引:5
Casey Frank A.; Sykes Donald H.; Craig Brian G.; Power Rosario; Mulholland H. Connor 《Journal of pediatric psychology》1996,21(3):335-352
Examined the behavioral adjustment at school age of 26 childrenwith surgically treated complex congenital heart disease comparedto that of 26 children who had been diagnosed as having an innocentmurmur. The children with complex heart disease were rated bytheir parents as more withdrawn, having more social problems,and engaging in fewer activities, and by their teachers as morewithdrawn. The families of the children with complex heart diseasereported experiencing more stress. Two variables, family strainand exercise tolerance, were strong predictors of teacher-ratedschool adjustment in the children with complex heart disease,with family strain accounting for 33% of the variance, and exercisetolerance 24%. The impact of the child's chronic condition onthe family thus seems to be a critical factor in the schooladjustment of these children, more so even than the physicallimitations imposed on the child by the chronic condition. 相似文献
12.
目的在使用目前儿童体外循环管路基础上,探讨自体血逆预充技术用于儿童体外循环对血液保护作用。方法选取60例体重在20~40kg之间体外循环下行择期心脏手术先心病患儿,分为自体血逆预充组(Rap组,n=30)和标准预充组(SP组,n=30)。自体Rap组在转机前进行Rap操作,对照组常规预充转机。记录所有患儿的一般临床资料、手术情况、术后监护室情况、不同时刻患儿红细胞压积(hematocrit,Hct)和围术期用血量。结果两组患儿一般资料和手术情况差异无统计学意义(P〉0.05);Rap组预充液量明显减少(P〈0.05);阻断升主动脉后10min时RAP组患儿Hct高于对照组(P〈0.05);Rap组术中用血量和输血率均少于SP组,但差异无统计学意义(P〉0.05),两组患儿术后恢复情况相比较差异无统计学意义(P〉0.05)。结论Rap技术用于儿童体外循环可以减少预充量,保持转机过程中较高的Hct。但对血液保护作用不明显,目前用于临床的儿童体外循环管路有待于进一步改进。 相似文献
13.
A Three‐Way Interaction among Maternal and Fetal Variants Contributing to Congenital Heart Defects
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Ming Li Jingyun Li Changshuai Wei Qing Lu Xinyu Tang Stephen W. Erickson Stewart L. MacLeod Charlotte A. Hobbs 《Annals of human genetics》2016,80(1):20-31
Congenital heart defects (CHDs) develop through a complex interplay between genetic variants, epigenetic modifications, and maternal environmental exposures. Genetic studies of CHDs have commonly tested single genetic variants for association with CHDs. Less attention has been given to complex gene‐by‐gene and gene‐by‐environment interactions. In this study, we applied a recently developed likelihood‐ratio Mann‐Whitney (LRMW) method to detect joint actions among maternal variants, fetal variants, and maternal environmental exposures, allowing for high‐order statistical interactions. All subjects are participants from the National Birth Defect Prevention Study, including 623 mother‐offspring pairs with CHD‐affected pregnancies and 875 mother‐offspring pairs with unaffected pregnancies. Each individual has 872 single nucleotide polymorphisms encoding for critical enzymes in the homocysteine, folate, and trans‐sulfuration pathways. By using the LRMW method, three variants (fetal rs625879, maternal rs2169650, and maternal rs8177441) were identified with a joint association to CHD risk (nominal P‐value = 1.13e‐07). These three variants are located within genes BHMT2, GSTP1, and GPX3, respectively. Further examination indicated that maternal SNP rs2169650 may interact with both fetal SNP rs625879 and maternal SNP rs8177441. Our findings suggest that the risk of CHD may be influenced by both the intragenerational interaction within the maternal genome and the intergenerational interaction between maternal and fetal genomes. 相似文献
14.
检测18例体外循环紫绀型先天性心脏病手术病人术前,术中及术后3,8天外周血血小数量和 附,聚集功能,探讨体外循环对血小板质和量的影响。结果显示,血小板数量和聚集功能在术后显著下降并持续至术后8天,血小板粘附功能显著下降,术后3天恢复。提示体外循环气血界面,人工材料非内皮表面可导致血小板激活,粘附,聚集面在量消耗,数量和功能显著下降。 相似文献
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16.
Oral‐facial‐digital syndrome type 1 in males: Congenital heart defects are included in its phenotypic spectrum
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Arjan Bouman Mariëlle Alders Roelof Jan Oostra Elisabeth van Leeuwen Nikki Thuijs Anne‐Marie van der Kevie‐Kersemaekers Merel van Maarle 《American journal of medical genetics. Part A》2017,173(5):1383-1389
Oral‐facial‐digital syndrome type 1 (OFD1; OMIM# 311200) is an X‐linked dominant ciliopathy caused by mutations in the OFD1 gene. This condition is characterized by facial anomalies and abnormalities of oral tissues, digits, brain, and kidneys. Almost all affected patients are female, as OFD1 is presumed to be lethal in males, mostly in the first or second trimester of pregnancy. Live born males with OFD1 are a rare occurrence, with only five reported patients to date. In four patients the presence of a congenital heart defect (CHD) was observed. Here, we report an affected male fetus with a hemizygous de novo mutation in OFD1 (c.2101C>T; p.(Gln701*)). Ultrasound examination demonstrated severe hydrocephalus, a hypoplastic cerebellum and a hypoplastic left ventricle of the heart. The pregnancy was terminated at 16 weeks of gestation because of poor prognosis. Post‐mortem examination of the fetus confirmed severe hypoplasia of the left ventricle of the heart. We emphasize that CHDs should be included in the phenotypic spectrum of OFD1 in males. This justifies molecular analysis of OFD1 when CHD is encountered prenatally in combination with one or more phenotypic features previously described in the OFD1 gene alteration spectrum. The underlying pathogenesis of CHD in OFD1 (and other ciliopathies) probably involves dysfunction of the primary cilia regarding coordination of left‐right signalling during early heart development. Whether these CHDs wholly or partly result from defective left right signalling, in which different types of cilia are known to play a critical role, remains a topic of research. 相似文献
17.
In a histological and fine structural study of right atrial biopsy specimens from 31 patients with rheumatic heart disease (RHD), aged 7 to 46 years, and 11 patients with congenital heart disease (CHD), aged 3 to 36 years, nerve fibers or endings were seen by electron microscopy in 11 specimens. There was concurrence of ordinary axons along with terminals bearing pale cholinergic or dark adrenergic synaptic vesicles. Smaller and denser cholinergic vesicles suggested proliferation followed by exhaustion of such nerve endings. The closest proximity of nerve terminal to muscle fiber was about 100 nm. In one RHD specimen a “specific terminal cell” was present between a nerve ending and muscle fiber; in another a possible neuromuscular contact was developing at the surface of a regenerating small muscle fiber with a few myofilaments. Unmyelinated axons amidst increased subendocardial and subepicardial collagen, with prominent fibroblasts and depleted muscle fibers, were seen more frequently in specimens of CHD. Loss of myofibrils and accumulation of mitochondria, with infrequent formation of lipofuscin bodies, characterized degenerating muscle fibers in CHD also, although to a lesser degree than in RHD (reported earlier, 1985). The myocardial blood vessels in CHD tended to have pale swollen endothelial cells and narrowed lumen. The most severely affected cases of CHD were those with (1) a very wide atrial septal defect (ASD), (2) ventricular septal defect (VSD) with vegetations near the defect, (3) 1 infundibular pulmonary stenosis, and (4) Fallot's tetralogy. 相似文献
18.
Sheng‐Wei Chang Mona Mislankar Chaitali Misra Nianyuan Huang Daniel G. DaJusta Steven M. Harrison Kim L. McBride Linda A. Baker Vidu Garg 《Human mutation》2013,34(9):1226-1230
The etiology for the majority of congenital heart defects (CHD) is unknown. We identified a patient with unbalanced atrioventricular septal defect (AVSD) and hypoplastic left ventricle who harbored an ~0.3 Mb monoallelic deletion on chromosome 3p14.1. The deletion encompassed the first four exons of FOXP1, a gene critical for normal heart development that represses cardiomyocyte proliferation and expression of Nkx2.5. To determine whether FOXP1 mutations are found in patients with CHD, we sequenced FOXP1 in 82 patients with AVSD or hypoplastic left heart syndrome. We discovered two patients who harbored a heterozygous c.1702C>T variant in FOXP1 that predicted a potentially deleterious substitution of a highly conserved proline (p.Pro568Ser). This variant was not found in 287 controls but is present in dbSNP at a 0.2% frequency. The orthologous murine Foxp1 p.Pro596Ser mutant protein displayed deficits in luciferase reporter assays and resulted in increased proliferation and Nkx2.5 expression in cardiomyoblasts. Our data suggest that haploinsufficiency of FOXP1 is associated with human CHD. 相似文献
19.
《Ultrastructural pathology》2013,37(4):413-431
In a histological and fine structural study of right atrial biopsy specimens from 31 patients with rheumatic heart disease (RHD), aged 7 to 46 years, and 11 patients with congenital heart disease (CHD), aged 3 to 36 years, nerve fibers or endings were seen by electron microscopy in 11 specimens. There was concurrence of ordinary axons along with terminals bearing pale cholinergic or dark adrenergic synaptic vesicles. Smaller and denser cholinergic vesicles suggested proliferation followed by exhaustion of such nerve endings. The closest proximity of nerve terminal to muscle fiber was about 100 nm. In one RHD specimen a “specific terminal cell” was present between a nerve ending and muscle fiber; in another a possible neuromuscular contact was developing at the surface of a regenerating small muscle fiber with a few myofilaments. Unmyelinated axons amidst increased subendocardial and subepicardial collagen, with prominent fibroblasts and depleted muscle fibers, were seen more frequently in specimens of CHD. Loss of myofibrils and accumulation of mitochondria, with infrequent formation of lipofuscin bodies, characterized degenerating muscle fibers in CHD also, although to a lesser degree than in RHD (reported earlier, 1985). The myocardial blood vessels in CHD tended to have pale swollen endothelial cells and narrowed lumen. The most severely affected cases of CHD were those with (1) a very wide atrial septal defect (ASD), (2) ventricular septal defect (VSD) with vegetations near the defect, (3) 1 infundibular pulmonary stenosis, and (4) Fallot's tetralogy. 相似文献