我国南,北方神经管缺陷病因学初探

对１９８６～１９８８年间监测的４１３４例神经管缺陷进行了病例对照（１：１）研究。对照为在同一医院紧接畸形儿出生的一例非畸形活产儿。采用非条件Ｌｏｇｉｓｔｉｃ回归方法控制混杂因素后，发现南北方神经管缺陷的发生均与母亲孕早期接触射线、噪声、化学物、农药有关。孕早期感冒并发热或不发热（南方、北方组）、服用磺胺（北方组）、避孕药（北方组）、中草药（南方、北方组）等亦可增加神经管缺陷发生的危险性。     

肥胖妇女有孕育神经管缺陷胎儿的危险

为了研究肥胖对妇女孕育神经管缺陷(Neural tube defect NTD)胎儿的危险性 ,我们对加利福亚地区肥胖妇女孕育 NTD胎儿的情况进行了一次大样本调查。从调查结果发现 ,肥胖妇女孕育 NTD胎儿的危险性要高于正常体重的妇女。其中 ,尤以孕育脊柱裂(Spina bifida)、颅脊柱裂 (Cranior     

山东省精神障碍患者生命质量及其相关因素

目的:了解山东省精神障碍患者的生命质量状况,分析其相关因素。方法:2015年,采用多阶段分层整群随机抽样在山东省开展第四次精神障碍流行病学调查。筛选符合精神障碍诊断与统计手册第4版诊断标准的精神障碍患者作为研究对象。采用一般情况调查表、匹兹堡睡眠质量指数量表、简易应对方式问卷、功能大体评定量表、生命质量量表进行调查。结果:农村居民(β=-0.96,P<0.01)、女性(β=-1.92,P<0.001)、未婚(β=-2.72,P<0.01)、农民/渔民(β=-0.94,P<0.05)、无业或失业(β=-1.93,P<0.01)患者生命质量得分更低,躯体健康状况(β=-5.59,P<0.001)和心理健康状况(β=-4.19,P<0.001)越差、匹兹堡睡眠质量指数(β=-0.49,P<0.001)越高,患者生命质量得分越低;积极应对(β=1.65,P<0.001)和功能大体评定量表(β=0.12,P<0.001)得分越高,患者生命质量得分越高。结论:精神障碍患者生命质量较差,应重点关注农村居民、女性、未婚、农民或渔民、无业或失业...     

神经管发育缺陷的研究进展

本文从流行病学研究、形态学研究和基因水平的研究几个不同层面对神经管发育缺陷的文献进行了回顾性分析,发现神经管畸形的发生与许多因素有关,如叶酸缺乏、环境因素等;在发生率上表现出明显的地域差异和时间差异;在研究方面,已有流行病学、形态学和基因水平的研究报道,但未见有神经管畸形的蛋白质表达的差异报道。     

神经管缺陷的病因学研究进展

脊柱裂、无脑儿和脑膜脑膨出通常被统称为神经管缺陷(neural tube defects,NTDs),是在神经胚形成过程中由于神经管闭合异常导致的中枢神经系统先天性疾病.其病因极其复杂,目前认为与神经管发育有关的基因异常和诸多环境因素均能导致NTDs,尽管很多学者对NTDs的病因做了大量的研究,但目前对于导致人NTDs的关键病因仍知之甚少.本文就目前研究最多的与神经管缺陷有关的基因和环境因素作一综述.     

神经管缺陷对气管上皮发育的影响研究

目的通过研究神经管缺陷对气管上皮发育的影响,探讨神经元与靶细胞或靶器官在发生发育过程中的相互作用。方法取脊柱裂胎儿的病变脊髓及其所对应部位气管,与同胎龄正常胎儿的相应结构制备组织切片,进行组织学观察和对比。结果正常胎儿在28w左右,气管上皮发育如成人;脊髓组织病理改变明显者,其所对应部位的气管上皮,细胞细小,细胞核小着色深,细胞顶部的纤毛短小,与正常作对照呈发育不良。结论胚胎时期神经元与靶细胞或靶组织在一定时间建立了相互联系,并相互影响着正常的进一步发育过程。     

同型半胱氨酸代谢相关基因与神经管缺陷的研究进展

神经管缺陷(neural tube defects,NTDs)是由于神经管的发生和分化紊乱而出现的人类出生缺陷中最常见和最严重的一组畸形。目前对其发病原因尚不清楚,一般认为是由环境因素和遗传因素共同作用造成的,目前研究的热点是同型半胱氨酸代谢相关因素与神经管缺陷的关系。本文对同型半胱氨酸代谢过程中某些关键酶和因子及其基因多态性与神经管缺陷的关系进行了综述。     

胎儿神经管缺陷畸形的产前超声诊断分析

目的探讨产前超声诊断胎儿神经管缺陷畸形的价值。方法回顾性分析经产前超声诊断的76例神经管缺陷畸形胎儿。结果无脑畸形26例,露脑畸形12例,脑膨出及脑膜膨出11例,单纯脊柱裂11例,无脑畸形合并脊柱裂5例,露脑畸形合并脊柱裂3例,脑膨出及脑膜膨出合并脑积水5例,脑膨出及脑脊膜膨出合并脊柱裂3例。结论超声作为一种安全简便的检查方法,只要熟悉掌握神经系统不同阶段的超声表现,规范化检查,注意追踪观察,就会大大提高神经管缺陷畸形的诊断正确率及早期发现率。     

神经管缺陷与Dishevelled基因表达的关系

神经管缺陷是复杂的多基因疾病,是中枢神经系统最常见的先天畸形。虽然其发病机制尚不清楚,但是研究已证实遗传因素与其发病具有相关性。本文将着重对Dishevelled基因细胞信号通路在神经管发育、神经管缺陷发病机制中的作用及有关Dishevelled基因的研究进展进行阐述。     

生育过神经管缺陷儿的妇女MTHFR基因C677T多态性与血浆Hcy水平测定

目的探讨MTHFR基因C677T多态性及血浆Hcy水平与神经管缺陷的关系。方法采用PCR-RFLP方法对30例生育过NTD患儿的母亲（NTD组）和34例生育过正常儿的母亲（对照组）进行MTHFR基因C677T等位基因检测,同时用高效液相色谱结合荧光检测法对两组母亲血浆中Hcy水平进行测定。结果NTD母亲组中VV基因型的频率为（36.7%）,V等位基因频率为（65.0%）,正常对照母亲组中VV基因型的频率为（17.6%）,V等位基因频率为（44.1%）,两组比较有显著性差异（P〈0.05）。NTD母亲组Hcy水平为（11.24±3.2）μmol/L,正常对照母亲组Hcy水平为（8.96±3.3）μmol/L,两组比较也有显著性差异（P〈0.01）。结论MTHFR基因C677T多态是神经管缺陷发病的遗传危险因素,它通过血浆中同型半胱氨酸水平升高而引起神经管缺陷。     

The thymic findings in stillborns with neural tube defects

Neural tube defects are among the most common congenital anomalies causing perinatal deaths. Other organ system anomalies may be associated with neural tube defects: for instance, various types of thymus pathology have been reported in these patients. In this study thymic changes were investigated in 30 stillborns with neural tube defects seen between January 1988 and June 1989. Thymic weights were significantly reduced in 14 cases and increased in 7. One patient had a double thymus, and in two cases no thymus tissue could be found. These findings suggest a primary developmental defect of the neural crest, affecting the orderly development of the thymus gland.     

Multigeneration maternal transmission in Italian families with neural tube defects

Periconceptional vitamin supplementation with folate prevents about three-quarters of expected cases of neural tube defects (NTDs) in clinical trials. However, vitamin action may be regulated at the level of the gene, and individual susceptibility to environmental agents, including dietary components, also may be under genetic control. We investigated the presence of familial factors in a retrospective case control study of neural tube defects in Genoa, Italy. Cases included all patients treated at a single pediatric neurosurgical service. Controls matched on age and sex came from the same hospital. We found strong evidence for the contribution of genetic factors in this study. There was an excess risk of 14 for the occurrence of NTDs in first-degree relatives compared to controls (P < .0005). There was no difference in sex ratio in any group of relatives, but maternal grandparents of children with a high spinal lesion had 14% fewer offspring than paternal grandparents (P < .005), possibly because of excess miscarriages. Our study is the first to show complex patterns of inheritance in spina bifida families affecting three generations in one clinical subgroup and preferentially on the mother's side. These results support a role for genomic imprinting and highlight the value of multidisciplinary epidemiologic and clinical studies that include multiple generations. New studies incorporating dietary and genetic approaches will help clarify and extend these findings. © 1996 Wiley-Liss, Inc.     

应用银染mRNA差异显示法寻找高温致神经管畸形差异表达基因

目的 :寻找高温致神经管畸形的差异表达基因。方法 :在高温致神经管畸形的动物模型上 ,分别于高温处理后 2 4、48和 72小时 ,提取鼠胚神经管组织总RNA和正常对照组鼠胚相应时间的神经管组织总RNA ,反转录合成cDNA第一链后进行差异显示PCR扩增 ,采用PAGE和银染技术显示差异条带 ,回收差异条带并经PCR二次扩增后 ,用点杂交方法筛除假阳性条带 ,再用Northern印迹杂交进一步鉴定。结果 :在高温致畸的鼠胚神经管组织中筛选到一个特别明显的差示cDNA片段N3 2 ,该片段所在基因在高温致畸的胚胎神经管组织中的表达远低于正常同龄胚的神经管组织。结论 :N3 2片段所在基因的低表达与高温致神经管畸形相关。     

Associated malformations among infants with neural tube defects

Infants with neural tube defects (NTDs) often have associated congenital anomalies. The reported frequency and types of associated malformations vary between different studies. The purpose of this investigation was to assess the frequency and types of associated malformations among infants with NTDs in a geographically well-defined population from 1979 to 2008 of 402,532 consecutive births. Of the 441 infants with NTDs born during this period, 20.4% had associated malformations. Infants with associated malformations were divided into those with recognizable conditions [11 (2.5%) infants with chromosomal and 23 (5.2%) with non-chromosomal conditions], and those without recognizable conditions [56 (12.7%) infants with multiple malformations]. Associated malformations were more frequent among infants with encephalocele (36.8%) than those with anencephaly (11.5%) or spina bifida (23.8%). Oral clefts and malformations in the musculoskeletal, renal and cardiovascular systems were the most commonly observed associated anomalies. The frequency of associated malformations in infants with NTDs emphasizes the need for a thorough investigation of these infants. Routine screening for other malformations, especially facial clefts and musculoskeletal, renal and cardiac anomalies, may need to be considered in infants with NTDs, and referral of these infants for genetics evaluation and counseling seems warranted.     

Date of conception and prevention of neural tube defects

The authors studied the time of conception of 280 fetuses and liveborns with anencephaly or spina bifida seen in a French Canadian population during a period of six years. There is an evident seasonal variation in the conception of NTD fetuses. Using a wave statistical model applied to data recorded over a six year period the authors have rejected the "no variation between the six two-month intervals" hypothesis at a P less than or equal to 0.005 level. It is postulated that, in any vitamin intake or environmental program to prevent NTD in families at risk, one must take into account the annual and seasonal variations, ethnic groups identity and the date of conception in the choice of control mothers.     

Sex,neural tube defects,and multisite closure of the human neural tube

While neural tube defects (NTD) overall have a female sex bias, this does not apply to all sites along the neuraxis. The findings regarding sex and NTD in a series of midtrimester fetuses are reviewed, and then analysed in terms of the recent hypothesis that during embryogenesis of the human neural tube there are multiple closure sites, rather than a single zipping up process. Females more often than males tend to have craniorachischisis, spina bifida involving the thorax, the holoacrania form of anencephaly, anencephaly and cervical spina bifida and encephalocoeles, while males more often than females have spina bifida affecting the lower spine. Meroacrania occurs equally in both sexes. Other sources indicate that there is a male bias in frontoethmoidal encephalocoeles. Since sex seems to be a factor that is differentially associated with lack of closure of specific areas of the neural tube, it would seem to support the notion that there are multiple closure sites in the human neural tube. However, no association was found between a particular sex and either the type of NTD which have an isolated abnormality or those NTD associated with developmental abnormalities of other body systems. © 1995 Wiley-Liss, Inc.     

Transcobalamins in the etiology of neural tube defects

In a sample of 79 pregnant women at risk offspring with neural tube defects (NTDs) and 158 controls, significantly increased median values were found for apo-transcobalamins I and II in amniotic fluid in the group at risk, thus confirming previous results. The findings may reflect a genetic disposition to NTDs associated with altered levels of apo-transcobalamins, and research on the etiology and mechanisms of NTDs should focus on these proteins.     

CD1+ cells in mothers of stillborn infants with neural tube defects

In healthy individuals, CD1+ cells are found in thymic tissue, but not in peripheral blood. The thymus, as a key organ of the neuroendocrine system, frequently shows gross abnormalities in infants with neural tube defects. In order to study the immuno-logic significance of fetal thymic findings, maternal T-lymphocyte subpopulations were investigated. In 10 mothers of healthy new-borns, 5 mothers of stillborn infants who had no gross abnormalities, and 5 mothers of stillborn infants with neural tube defects, CD1+, CD3+, CD4+, and CD8+ cells were studied. Only the mothers of the infants with open neural tube defects showed CD1 + cells in their peripheral blood. © 1995 Wiley-Liss, Inc.     

Contribution of VANGL2 mutations to isolated neural tube defects

Kibar Z, Salem S, Bosoi CM, Pauwels E, De Marco P, Merello E, Bassuk AG, Capra V, Gros P. Contribution of VANGL2 mutations to isolated neural tube defects. Vangl2 was identified as the gene defective in the Looptail (Lp) mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity (PCP) pathway, also called the non‐canonical Frizzled/Dishevelled pathway, which mediates the morphogenetic process of convergent extension essential for proper gastrulation and neural tube formation in vertebrates. Genetic defects in PCP signaling have strongly been associated with NTDs in mouse models. To assess the role of VANGL2 in the complex etiology of NTDs in humans, we resequenced this gene in a large multi‐ethnic cohort of 673 familial and sporadic NTD patients, including 453 open spina bifida and 202 closed spinal NTD cases. Six novel rare missense mutations were identified in seven patients, five of which were affected with closed spinal NTDs. This suggests that VANGL2 mutations may predispose to NTDs in approximately 2.5% of closed spinal NTDs (5 in 202), at a frequency that is significantly different from that of 0.4% (2 in 453) detected in open spina bifida patients (p = 0.027). Our findings strongly implicate VANGL2 in the genetic causation of spinal NTDs in a subset of patients and provide additional evidence for a pathogenic role of PCP signaling in these malformations.