Social networks and risk of neural tube defects

The contribution of social support and social networks to risk of neural tube defects (NTDs) has not been explored, despite evidence that various aspects of the social environment contribute to their etiology. Using data from a population-based case–control study of deliveries occurring in California from 1989 to 1991, this study investigates whether social networks, as measured by the presence and frequency of various types of social contacts, are associated with NTD risk. In-person interviews were conducted with 538 (88% of eligible) mothers of NTD cases and with mothers of 539 non-malformed controls (88%) on average 5 months from the term delivery date. Unadjusted results indicate that women who reported having close friends, close relatives, or monthly contacts with close friends or relatives had 30–70% lower risks of having NTD-affected pregnancies, relative to women reporting none to any of these measures. Only the presence of close friends was associated with reduced NTD risk after adjustment for other aspects of the social network and several potential covariates. This study is the first to investigate the association between social networks and risk of NTDs. Stronger inferences await replication and extension of these results.     

神经管畸形的地理影响因素分析

神经管畸形（NTD）是一种严重的出生缺陷。我国NTD总发生率呈现出地理聚集性特征。现就影响NTD空间分布的地理因素进行探讨。     

出生儿神经管缺陷发病相关因素的病例对照研究

目的 探讨山西省出生儿神经管缺陷发生的相关因素，为进一步采取干预措施提供科学依据。方法 采用1：1配比的病例对照研究，对217例神经管缺陷患儿的母亲和217例非患儿的母亲进行回顾性调查。结果 经多因素条件logistic回归分析，神经管缺陷发病的危险因素为有出生缺陷儿既往史（OR=12．85），孕期接触化肥（OR=3．40）、服用磺胺类药物（OR=12．72）和丈夫吸烟（OR=2．10）；保护因素为胎龄（OR=0．65）。结论 既往生产缺陷儿史、本次妊娠早期接触化学物质、服用磺胺类药物和丈夫吸烟可能使神经缺陷发生的危险性增加。     

309例神经管缺陷围产儿相关因素研究

目的:描述1998~2003年期间辽宁省围产儿神经管缺陷(NTDs)的特征及变化趋势。方法:以医院为基础的监测方法。结果:辽宁省累计NTDs发生率9.99/万,其中男性6.95/万,女性13.15/万,城市5.96/万,农村17.35/万。无脑畸形发生率6年下降73.19%。母龄别发生率为25~29岁组发生率最低;孕妇末次月经在8、9月时出生的男性NTDs高发。NTDs围产儿早产占51.78%,低出生体重占46.92%,围产期病死率为75.08%。结论:辽宁省围产儿NTDs发生率女性高于男性,农村高于城市。男性NTDs发生有季节性流行趋势。NTDs儿围产期病死率高,预后差。加强药物预防、科普宣教和产前诊断是降低其发生率的有效措施。     

中国神经管畸形高低发地区季节及性别分布特征

目的：分析中国高低发区神经管畸形(NTDs)的流行病学分布特点。方法：利用1992—1994年期间“中美预防神经管畸形合作项目”监测资料，按照国际上采用的脊柱裂高低位不同损害水平分类方法，将NTDs分为四类，即无脑畸形、脑膨出、高位和低位脊柱裂(SB)，同时再将每一类按照是否合并其他畸形分为单纯与合并型，比较中国南北方、城乡、季节、性别NTDs发生率。分析中对城乡、季节、NTDs种类、性别分别进行调整，计算调整率。结果：32 6874名新生儿(包括孕20周及以上的活产、死胎和死产)中，NTDs 784例，北方NTDs发生率为5．57‰，南方为0．88‰。各类NTDs发生率存在南北方差别(P＜0．01)。调整其他影响因素后，北方总NTDs发生率大约是南方的3—7倍；NTDs发生率存在城乡差别(P＜0．01)，调整后北方农村NTDs发生率大约是城市的3—4倍，调整后南方农村NTDs发生率大约是城市的1．6—1．9倍；北方高位阳发生率在9—11月有季节性升高现象，南方无脑畸形率9—11月低于其他季节，其他类型NTDs在南北方无明显季节变化。结论：中国北方是世界上NTDs高发地区。NTDs发生率存在南北方、城乡差别，北方高位阳发生率有季节升高现象。不同类型NTDs之间在流行病学特征和表型上存在病因异质性。     

山西省神经管畸形影响因素的病例对照研究

目的 探索山西省神经管畸形(NTDs)患儿发生的影响因素.方法 采用1:1匹配的病例对照研究设计,对医院收集的病例组和对照组孕妇进行问卷调查,采集肘静脉血标本2 ml,检测亚甲基四氢叶酸还原酶(MTHFR)基因多态性.使用条件logistic回归模型,对MTHFR基因及其他因素进行单因素及多因素分析,筛选山西省NTDs患儿发生的影响因素.结果 MTHFR基因677位点有3种基因型,即野生型CC、杂合突变型CT和纯合突变型TT,3种基因型在病例组和对照组间分布差异有统计学意义(χ=2=14.61,P=0.001),病例组T等位基因频率(60.6%)高于对照组(41.4%),差异有统计学意义(χ=2=14.59,P<0.001).经单因素条件logistic回归分析有统计学意义的变量15项引入多因素条件logistic回归,最终进入模型的变量有4项,分别为既往孕次(OR=2.87,95%CI:1.28～6.44)、孕早期接触化肥(OR=16.18,95%CI:1.18～221.59)和经常食用发芽土豆(OR=4.66,95%CI:1.78～12.17)以及MTHFR基因677位点突变(OR=2.13,95%CI:1.08～4.21).结论 孕次、孕早期接触化肥、食用发芽土豆和MTHFR基因677位点突变是山西省NTDS患儿发生的主要危险因素.     

2007 - 2016年河南省神经管缺陷发生率变化趋势分析

目的 分析2007 - 2016年河南省神经管缺陷（NTDs）的发生率变化,为制定神经管缺陷防控措施提供依据。方法 按照中国出生缺陷医院监测方案对2007 - 2016年河南省75家监测医院出生（包括引产）的围产儿进行出生缺陷监测,并对监测所得的神经管缺陷资料进行回顾性分析。结果 2007 - 2016年河南省75所监测医院共监测围产儿2 285 027人,NTDs 2 145例,NTDs总发生率9.39/万,其中无脑畸形、脊柱裂、脑膨出的总发生率分别为2.70/万、5.27/万和1.41/万。NTDs年度发生率从2007年的15.60/万下降到2016年的6.98/万,降幅达55.26%（χ2 = 12.513, P＜0.001）。NTDs在孕28周前检出的比例由2007年的30.08%上升到2016年的78.87%（χ2 = 14.038, P＜0.001）。NTDs总发生率女性（9.27/万）高于男性（8.16/万）（χ2 = 8.047,P = 0.005）,乡村（9.80/万）高于城镇（8.65/万）（χ2 = 7.343,P = 0.007）,产妇年龄＜20岁组NTDs总发生率最高,其次为≥35岁组,25～29岁组最低,呈“U”形分布。结论 河南省神经管缺陷年度发生率呈下降趋势,但仍处于较高水平,脊柱裂是最主要的神经管缺陷类型。     

内皮型一氧化氮合酶基因多态性与神经管畸形的关系

目的:探讨内皮型一氧化氮合酶基因第4内含子27bp长度的可变数目串联重复序列(VNTR)4a/bVNTR基因多态性和第7外显子单核苷酸多态性G894T与神经管畸形的关系。方法:提取2008年1月～2009年9月间生育神经管畸形儿的30名妇女和同期生育正常儿的60名健康妇女基因组DNA,用PCR-RFLP方法测定G894T和4a/bVNTR的多态性。结果:①eNOS基因G894T位点在本次研究中有3种基因型,即野生型GG、纯合突变型TT和杂合突变型GT。其基因型频率(GG、GT、TT)在病例组中的构成分别为46.67%、40.00%、13.33%,在对照组中的构成分别为73.33%、21.67%、5.00%,两组间的差异有统计学意义(χ2=6.413,P0.05);其等位基因G的频率在病例组和对照组中的构成分别为66.7%和84.2%,T等位基因的频率分别为33.3%和15.8%,差异有统计学意义(χ2=7.218,P0.01);②eNOS基因4a/bVNTR位点在本次研究中有两种基因型,即bb型和ab型。其基因型频率(bb、ab)在病例组中的构成分别为63.33%和36.67%,在对照组中的分布频率分别为80.00%和20.00%,在两组中的差异无统计学意义(P0.05);其等位基因b的频率在病例组和对照组中的构成分别为81.7%和90.0%,a等位基因在病例组和对照组中的分布频率分别为18.3%和10.0%,差异无统计学意义(P0.05);结论:母亲eNOS基因894位点G→T突变是出生神经管畸形儿的独立遗传学因素,而第4内含子27bpVNTR基因突变不足以构成导致神经管畸形发生的独立遗传学因素。     

中国神经管畸形儿在高发和低发区的性别分布及其出生结局

目的 对中国神经管畸形(NTD)高发和低发区畸形儿的性别及出生结局的流行病学特点进行描述性分析。方法 利用1992～1994年期间“中美预防神经管畸形合作项目”监测资料,按照国际上采用的分类方法,将NTD分为4类,即无脑畸形、脑膨出、高位和低位脊柱裂,再将每一类按照是否合并其他系统畸形分为单纯与合并型,进行高低发区不同类型NTD的男女性别率、性别率比和出生结局的研究,调整城乡、季节和种类,计算调整后的性别率。结果 共监测到326874总产数(包括孕20周及以上的活产、死胎和死产),NTD784例,北方高发区女性无脑畸形发生率(1．30／1000女性总产数)和高位脊柱裂发生率(3．99／1000女性总产数)高于男性(0．66／1000男性总产数和1．66／1000男性总产数),其调整率女性大约是男性的1．8～2．1倍;南方低发区女性高位脊柱裂发生率(0．32／l000女性总产数)和低位脊柱裂发生率(0．21／1000女性总产数)高于男性(0．10／1000男性总产数和0．09／1000男性总产数),其调整率女性是男性的1．3～1．6倍;单纯NTD占全部病例的80％以上,并且单纯NTD女性发生率(2．57／1000女性总产数)显著高于男性(1．40／1000男性总产数),合并型：NTD男女性别发生率(0．36／1000和0．49／1000)的差异无显著性;死产中以高位脊柱裂(44．95％)、活产中以低位脊柱裂(40．64％)占比例较高。死胎中高位脊柱裂和无脑畸形分别占47．06％和35．56％。结论 南方低发区和北方高发区性别率差异随NTD种类而不同,提示可能存在随NTD率增高,女性高位脊柱裂和无脑畸形所占比例有增大趋势。无脑畸形、高位与低位脊柱裂之间可能存在不同的遗传和环境因素。     

1996～2000年全国神经管缺陷的动态监测

目的：利用1996年1月至2000年12月期间中国出生缺陷监测网收集的资料,描述国产儿无脑,脊柱裂和脑膨出3种神经管缺陷（NTDs)的流行病学特征及其动态变化趋势。方法：采用以医院为基础的监测方法收集资料,调查对象为孕28周至产后7d住院分娩的围产儿,包括活产,死胎和死产。结果：共收集围产儿2218616列;神经管缺陷儿2873例。中国人围产儿NTDs总发生率为12．95／万,其中无脑,脊柱裂和脑膨出的发生率分别为5．02／万,6．30／万和1．64／万,总的NTDs和无脑畸形年度发生率呈下降趋势,男性NTDs发生率为9．75／万,女性的15．96／万,城市为7．76／万,农村为25．20／万,北方为19．90／万,南方为5．81／万,母龄别发生率在＜20岁和＞30岁组高于其他年龄组。NTDs围产儿早产占50．9％,低出生体重占50．6％,围产期病死率为77．8％。结论：中国围产儿NTDs发生率女性高于男性,农村高于城市,北方高于南方。年度发生率呈下降趋势,但高于其他国家同期水平。神经管缺陷儿出生素质差,围产期病死率高,预后不良。加强预防和产前诊断是降低发生率的有效措施。     

Economic burden of neural tube defects in Germany

Objective

Failure of closure of the neural tube often leads to serious malformations, including spina bifida, anencephaly and encephalocoele. Despite improvements in medical and surgical treatment, the burden associated with spina bifida is substantial but country-specific data are lacking outside North America. This study aims to improve understanding of the economic implications and burden associated with the morbidity of children and adults with neural tube defects (NTDs) in Germany.

Study design

Retrospective data analysis.

Methods

2006–2009 German health insurance data of persons with NTDs (spina bifida and encephalocoele) were analysed to determine the economic burden of illness associated with NTDs in Germany. Cases were identified using ICD-10 codes; data included outpatient and inpatient care, rehabilitation, remedies and medical aids, pharmacotherapy use, long-term care and information on sick leave. The analysis was stratified by age group to provide a burden estimate specific to a person's age. To obtain an indicator of incremental burden to the Statutory Health Insurance (SHI), results were compared to the standardized healthcare expenditures according to the German Risk Compensation Scheme (RSA).

Results

Overall, 4141 persons with an ICD code related to NTDs were identified (out of a population of 7.28 million persons screened). The administrative prevalence ranged from 0.54 to 0.58 per 1000 enrollees. Of those, 3952 (95.4%) were diagnosed with spina bifida. The average annual mean healthcare expenditure of persons with spina bifida was €4532 (95% CI = 4375–4689, SD = 9590, Median = 1000), with inpatient care contributing €1358 (30.0%), outpatient care €644 (14.2%), rehabilitation €29 (0.6%), pharmacotherapy €562 (12.4%), and remedies and medical aids €1939 (42.8%). The incremental cost due to spina bifida was substantially higher than the standardized SHI expenditures for all age groups. The difference was highest for persons ≤10 years old (€10,971 vs €2360 for the age group ≤1, €8599 vs €833 for the age group 2–5 years and €10,601 vs €863 for the age group 6–10 years). The difference was smallest for the age group 41–50 years (€2524 vs €1101) and for 71 years and over (€5278 vs €4389).

Conclusion

Expenditures of persons with spina bifida exceeded the standardized SHI expenditures, indicating a considerable economic burden. The economic burden is continuous throughout the person's life, with high monetary impact and exposure to the healthcare system (especially in early years of life). Efforts should be devoted to improve the prevention of NTDs and provide appropriate support for persons with NTDs, parents, and caregivers—especially in early years.     

微量元素与神经管畸形关系的病例对照研究

目的探讨多种微量元素与神经管畸形的关系,及其他危险因素。方法采用1：1配比的病例对照研究方法,在“中美出生缺陷监测系统”中,募集新近发生的88对神经管畸形病例和对照,问卷调查出生缺陷其他已知危险因素的暴露情况;采用微波消化、原子吸收、ICP质谱分析等方法,测定了病例和对照孕妇怀孕早期阶段,毛发中必需微量元素（铬、锰、铜、锌、钴、钼）、毒性元素（铅、砷、镉、汞）以及部分稀土元素（钇、镧、镨、钕）的含量;用Cox比例风险模型进行了流行病学多因素分析。结果孕期发热是神经管畸形的危险因素（OR=6．525,P=0．034）,而孕妇早期发锌含量（OR=0．541．g／100g,P=0．02）和产前检查次数（OR=0．634,P〈0．001）作为保护性因素保留在多因素模型中。结论孕早期锌缺乏可能是神经管畸形的原因之一,避免孕早期发热性感染,以及定期产前检查,可降低神经管畸形的发生率。     

母亲饮食因素与神经管畸形危险性的病例对照研究

目的探讨母亲饮食因素在神经管畸形（NTD）发病中的作用。方法选择山西省出生缺陷高发的平定、昔阳、太谷和泽州4个县，进行以人群为基础的出生缺陷病例对照研究。病例为2003年1月至2005年6月在4个县监测到的363例NTD病例，对照为同期在同地区出生的523名无体表畸形的健康婴儿。结果单因素分析结果表明，与NTD发生有关的饮食因素有食用肉类、蛋奶、豆类、腌菜、发芽土豆、食物烹调习惯、饮用水水源类型、饮啤酒、红酒或米酒和饮茶。在调整妇女文化程度和畸形生育史的基础上，多因素logistic回归分析表明，肉类和豆类为NTD的保护因素，NTD的危险性随着肉类、豆类食用频率的增加逐渐下降，其在人群中的归因危险度（PAR）分别为69．4％和22．0％。食用腌菜为危险因素，NTD危险性随着腌菜食用频率增加而显著增加，具有明显的剂量反应关系，其PAR值为18．5％。此外，饮用河水或池塘水的妇女较饮用井水或自来水者的危险性增高（OR=3．42，95％CI：1．44～8．09），每天饮茶者较不饮或偶尔饮茶妇女的危险性增高（OR=4．65，95％CI：1．41～15．36），但二者PAR值较低，分别为4．7％和2．6％。结论富含叶酸的肉类和豆类对NTD发生具有显著的保护作用。怀孕前后食用腌菜、饮用河水或池塘水以及每天饮茶是NTD的危险因素。     

叶酸配伍大豆异黄酮对大鼠神经管畸形的影响

目的研究不同剂量叶酸配伍大豆异黄酮对神经管畸形孕鼠体内过氧化状态的影响。方法采用正交设计方案来观察叶酸和大豆异黄酮在不同的配伍干预下对环磷酰胺致神经管畸形(脑膨出为主)的孕鼠体内重要的抗氧化物质谷胱甘肽及其酶以及一些与抗氧化相关元素水平的影响。将100只鼠龄25～3个月的孕鼠随机分为对照组、模型组、配伍干预组和单独干预组。孕20d时,处理孕鼠并进行血中谷胱甘肽、谷胱甘肽过氧化物酶及元素硒、锰、铁抗氧化相关指标的检测;剖腹取出胎鼠,统计其畸形发生率。结果叶酸配伍大豆异黄酮的交互作用对血中谷胱甘肽、谷胱甘肽过氧化物酶及元素硒、锰、铁等抗氧化相关指标的水平均产生了影响,且两者之间的配伍关系对抗氧化相关指标的影响随配伍的不同而表现不同。研究结果显示,叶酸07mg/kg配伍大豆异黄酮160mg/kg的干预效果最佳;与叶酸或大豆异黄酮的2倍剂量(叶酸14mg/kg、大豆异黄酮320mg/kg)进行单独干预比较,结果显示配伍干预效果要优于单独干预效果。结论叶酸是预防神经管畸形发生的主要因素,而大豆异黄酮加强了体内抗氧化能力,有可能增强叶酸的保护作用而使神经管畸形的发生率下降,而增强效果的发挥依赖于最佳配伍的选择。     

母亲解偶联蛋白(UCP2)基因多态性与后代神经管畸形的关系

目的:探索山西省母亲解偶联蛋白(UCP2)基因多态性与后代神经管畸形发生的关系。方法:采用1:1配对病例对照研究方法,对山西省116例曾孕育过NTDs患儿的母亲和116例配对的未孕育过任何畸形患儿的母亲采血并进行UCP2基因的多态性分析。结果:病例组母亲3’末端缺失纯合子基因型D/D显著高于对照组母亲(P0.01),而A55V基因多态性与NTDs无相关(P0.05)。结论:母亲UCP2基因第8外显子45bpD/I多态性可能是后代发生神经管畸形的遗传危险因素。     

泽州县2003～2004年神经管畸形的流行状况

目的了解泽州县目前神经管畸形患病水平及流行特征,为今后制定本县出生缺陷的预防措施提供依据。方法以人群为基础,对泽州县26个乡镇所有在本地长期居住的妇女所分娩的孕20周及以上到生后7d的胎儿和新生儿进行监测。结果2003年1月至2004年12月,共监测到孕满20周及以上的出生7992名,发现NTDs病例128例,NTDs出生患病率为160.2/万,其中无脑儿为72.6/万(58/7992)、脊柱裂为81.3/万(65/7992)、脑膨出为6.3/万(57992)。NTDs占全部体表重大出生缺陷病例的71.5%(128/179)。NTDs的患病率与母亲年龄、文化程度及妊娠胎数显著相关。母亲年龄<20岁或≥30岁、文化程度为小学及以下、双胎或多胎的妊娠妇女中NTDs的出生患病率显著升高。结论我县NTDs出生患病率处于我国乃至世界最高的水平。文化程度低、怀孕年龄太小或较大以及多胎妊娠的妇女生育神经管畸形患儿的危险性较大。积极推动孕前保健各项措施,有望有效降低我县NTDs发生率。     

Periconceptional maternal fever,folic acid intake,and the risk for neural tube defects

PurposePrevious studies have shown an association between maternal fever in early pregnancy and neural tube defects (NTDs) such as spina bifida. Periconceptional folic acid intake has been shown to reduce the risk of these outcomes.MethodsUsing data from the Slone Epidemiology Center Birth Defects Study (1998–2015), we examined the impact of folic acid on the relationship between maternal fever in the periconceptional period (28 days before and after the last menstrual period) and NTDs. Logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsMothers of 375 cases and 8247 nonmalformed controls were included. We observed an elevated risk for NTDs for fever in the periconceptional period (OR: 2.4; 95% CI: 1.5–4.0). This association was weaker for mothers who reported consuming the recommended amount of folic acid (≥400 μg per day; OR: 1.8; 95% CI: 0.8–4.0) than mothers with low folic acid intake (<400 μg per day; OR: 4.2; 95% CI: 2.2–8.2).ConclusionsOur data support an association between maternal periconceptional fever and an increased risk for NTDs and also provide evidence that this association was attenuated for mothers who reported consuming folic acid at recommended levels in the periconceptional period.     

维生素B12在神经管缺陷一级预防中的作用研究进展

维生素B12(Vit B12)又称钴胺素(cobalamins),是一组有钴结合咕啉环的红色类咕啉化合物的总称,是一种维持人体正常代谢和机能不可缺少的、机体不能合成的微量营养素.自1980年Schorah等[1]报道低水平Vit B12和脑畸形发生有关后,Vit B12与神经管缺陷(neural tube defects,NTDs)的关系引起广泛关注.近年来,NTDs的一级预防干预措施主要是在育龄妇女中推广增补叶酸,然而目前越来越多的学者呼吁应在增补叶酸的基础上同时增补Vit B12,以进一步降低NTDs发生率[2-5].本文对近年来国内外Vit B12与NTDs的相关文献以及增补Vit B12所面临的问题予以综述,以期为NTDs一级预防及相关问题的进一步研究提供参考.     

Investigation of ultrasound screening efficiency for neural tube defects during pregnancy in rural areas of China

Objectives

To understand the uptake and efficacy of ultrasound screening for neural tube defects (NTDs) during pregnancy, and the outcomes when NTDs were detected in rural areas of China.

Study design

Prevalence study.

Methods

Four hundred and twenty-four women who delivered or gestated babies/fetuses with NTDs were selected at random in 20 counties of two provinces of China from March 2008 to January 2009. The uptake of ultrasound screening, NTD detection rate and termination of pregnancy (TOP) rate were calculated and analyzed. Generalized estimating equations were employed to control for potential confounding factors.

Results

The uptake of ultrasound screening was 98.8%. Among the study subjects, 361 (85.1%) NTDs were detected and 63 (14.9%) were not detected by prenatal ultrasound screening. The total detection rate was 43.3% (15.6%, 49.6% and 52.2% in the first, second and third trimesters, respectively; P < 0.05). Taking the possibility of NTD detection in the first trimester as 1.0, the possibilities in the second and third trimesters were 10.9 [95% confidence interval (CI) 6.5–18.3] and 25.2 (95% CI 13.3–47.6), respectively. The detection rate at the township health centres (THCs), family planning centres (FPCs), maternal and child care service centres (MCSCs) and hospitals was 24.5%, 29.1%, 53.6% and 78.1%, respectively (P < 0.05). Taking the possibility of NTD detection at THCs as 1.0, the possibilities at FPCs, MCSCs and hospitals were 0.9 (95% CI 0.5–1.6), 3.4 (95% CI 1.9–6.1) and 2.1 (95% CI 1.3–3.4), respectively. Three hundred and fifty-five (98.3%) of the 361 NTDs detected at prenatal ultrasound screening ended in TOP.

Conclusions

The uptake of ultrasound screening was satisfactory, but the NTD detection rate was low. Ultrasound screening did not play its full role in the secondary prevention of NTDs in the study areas. Medical institutions in rural areas in China need to improve their ultrasound screening skills in order to increase the efficacy of NTD control.     

Scribble基因体细胞突变与神经管缺陷的关联研究

目的筛选中枢神经系统病变组织中神经管缺陷(NTDs)发病相关的Scribble(SCRIB)基因的突变位点,并探讨突变来源,鉴定其是否为体细胞突变。方法用Ion Personal Genome Machine(PGM)测序技术检测28例NTDs患儿病变处和脐带组织DNA,筛选体细胞突变位点,并用Sanger测序对病变处和脐带、皮肤、心脏、肌肉、胸腺和肺组织DNA进行测序。进一步扩大样本量(51例病例)验证已发现突变。结果对28名NTDs患儿进行PGM测序,在1例患儿病变处检测到c.1931GC突变;另1例患儿病变处检测到c.1265CT突变;在该2名患儿脐带组织中未检测到相应的突变,提示c.1931GC和c.1265CT为体细胞突变。其中1名患儿用Sanger法测序在皮肤、心脏、肌肉、胸腺和肺组织均检测到c.1931GC突变;另1名患儿的各非病变组织均未检测到c.1265CT突变。扩大样本量研究没有检测到c.1931GC突变;在5名患儿的病变处及各非病变组织中均检测到c.1265CT多态性变异,提示此突变在这5名患者中可能来源于父母。结论 NTDs的发生不仅与SCRIB基因来源于父母的突变有关,还与体细胞突变有关,体细胞突变理论可为NTDs发生的遗传机制提供新的思路。