不明原因儿童惊厥性癫痫持续状态患者基因筛查及临床分析

目的 观察儿童患者中不明原因惊厥性癫痫持续状态发生癫痫相关基因突变的比例及类别,并分析其发病特点.方法 收集2017年1月至2020年12月在西安交通大学第二附属医院及西北妇女儿童医院儿童神经内科就诊的85例不明原因惊厥性癫痫持续状态患儿的资料,回顾性分析癫痫患儿相关基因检查结果及发病特点.结果 不明原因惊厥性癫痫持续状患儿中癫痫相关基因突变占比为54.12％(46/85);癫痫相关突变基因主要为SCN1A基因,所占比例为47.83％(22/46),其次为SCN9A、GRIN2A、CNCNA1A和KCNQ2基因突变,所占比例依次为15.22％(7/46)、6.52％(3/46)、6.52％(3/46)和4.35％(2/46),其余占比均为2.17％(1/46);基因突变患者和未发生基因突变患者的发作持续时间和发作频率差异均无统计学意义(P>0.05),发病年龄(Z=-3.497)、生长发育情况(χ2=5.695)差异均有统计学意义(P<0.05).结论 不明原因儿童癫痫持续状态患儿中癫痫相关基因突变在病因中占较大比例,基因突变导致的儿童患者发病年龄早于其他病因,且生长发育受到一定影响.     

1型糖尿病相关单基因自身免疫性综合征临床进展

自身免疫反应破坏胰岛β细胞功能是1型糖尿病(T1DM)的重要病因,一些单基因自身免疫性综合征可伴有不同程度的T1DM发生,这是深入认识自身免疫和T1DM的重要疾病模型。本文对已知的8种与T1DM相关的单基因自身免疫性综合征的诊断、治疗、遗传检测等方面作综述,为T1DM的诊疗拓展思路。     

难治性癫痫患者脑内HIF-1α与多药耐药基因1表达的相关性及其意义

目的：探讨难治性癫痫患者脑内缺氧诱导因子-1α（HIF-1α）与多药耐药基因1（MDR1）的表达情况、相关性及其意义。方法：收集9例难治性癫痫组手术切除脑组织标本及7例对照组脑组织标本,采用免疫组织化学染色方法检测HIF-1α和MDR1的表达情况,并分析HIF-1α与MDR1表达阳性率的相关性。结果：HIF-1α在难治性癫痫组脑组织中的阳性表达率77.8%（7/9）明显高于对照组的14.3%（1/7）;MDR1在难治性癫痫组脑组织中的阳性表达率66.7%（6/9）明显高于对照组的14.3%（1/7）,比较差异均有统计学意义（P〈0.05）;难治性癫痫组脑组织中HIF-1α与MDR1的表达呈正相关（r=0.76,P〈0.05）。结论：难治性癫痫患者脑内HIF-1α和MDR1表达升高,且两者呈正相关。HIF-1α可能通过调控MDR1基因表达而参与难治性癫痫的形成。     

癫痫性精神障碍94例临床分析

94例确诊的癫痫性精神障碍，男性为女性的2.2倍，盲和小学化占大多数（66.02%），36.50%的成年患未婚，农民患占59.57%，提示经济化落后，卫生保健水平低，造成产伤、感染，是癫痫的重要发病因素。本组15例有家庭精神病史（15.96%），13例有癫痫病史（13.83%），提示遗传与癫痫有密切关系。其中慢性癫痫性精神障碍，平均在首次癫痫发作后9.4年出现精神症状，是癫痫发作导致脑损害的结果，支持因果学说。本病的治疗与家族史、脑电图异常无密切关系，抗癫痫药治疗为主，抗精神病药物治疗为辅；长期坚持服药，有效地控制癫痫发作，是防治癫痫性精神障碍的关键。     

癫痫性精神障碍的临床分析

目的研究药物治疗联合心理治疗对癫痫性精神障碍患者的临床疗效,为临床提供参考。方法选择癫痫性精神障碍患者102例,根据患者情况给药进行药物治疗,卡马西平开始时每日0.2⁰.4 g,以后每周逐渐增加至最大量每日1.6 g。一般分30.4 g,以后每周逐渐增加至最大量每日1.6 g。一般分3⁴次服用。通常成年人的限量,124次服用。通常成年人的限量,12¹5岁,每日不超过1.0 g,15岁以上一般每日不超过1.2 g。丙戊酸钠成人常用量:每日按体重15 mg/kg或每日60015岁,每日不超过1.0 g,15岁以上一般每日不超过1.2 g。丙戊酸钠成人常用量:每日按体重15 mg/kg或每日600¹ 200 mg分次21 200 mg分次2³次服。开始时按53次服。开始时按5¹0 mg/kg,一周后递增,至能控制发作为止。当每日用量超过2 500 mg时应分次服用,以减少胃肠刺激。每日最大量为按体重不超过30 mg/kg、或每日1.810 mg/kg,一周后递增,至能控制发作为止。当每日用量超过2 500 mg时应分次服用,以减少胃肠刺激。每日最大量为按体重不超过30 mg/kg、或每日1.8².4 g。苯妥英钠成人口服,每次100 mg,22.4 g。苯妥英钠成人口服,每次100 mg,2³次/日,饭后服用,数日后逐增至600 mg/d,稳定后用维持量。儿童,每日5 mg/kg,最大量为300 mg/d,维持量为43次/日,饭后服用,数日后逐增至600 mg/d,稳定后用维持量。儿童,每日5 mg/kg,最大量为300 mg/d,维持量为4⁸ mg/kg。同时,进行心理治疗,观察治疗前后患者的精神障碍(感知障碍、意识障碍、情感障碍、行为障碍、人格改变)变化情况并根据患者恢复情况进行疗效评定;根据《癫痫患者生活质量量表-31》评分,分别在患者入院时和治疗完成半年后进行随访,分别对发作担忧、生活满意度、情绪、精力、认知能力、社交能力、药物影响方面进行评分,对比治疗前后的评分结果。结果 102例患者治疗后,患者的精神障碍(感知障碍、意识障碍、情感障碍、行为障碍、人格改变)例数都明显减少,根据患者恢复情况评定其疗效显示:治愈33例,占32.35%;好转31例,占30.39%;进步33例,占32.26%;无效5例,占4.90%;总有效率为95.10%。治疗结束半年后随访发现病人在发作担忧、生活满意度、情绪、认知能力、社交能力和药物影响方面与进行治疗前都得到了明显提高。结论治疗癫痫性精神障碍应根据患者病情程度在药物治疗癫痫病的基础上,加以心理治疗,加强患者对治疗的积极性和康复自信心,提高患者的生活质量,提高患者的康复率。     

性发育异常患者遗传学特点与临床表型分析

目的 探讨染色体核型及SRY基因检测对性发育异常(DSD)的临床诊断价值.方法 回顾性分析332例DSD的染色体核型、SRY基因和临床表型,染色体核型采用外周血淋巴细胞培养G显带分析,SRY基因采用PCR技术扩增.结果 332例DSD患者中检出异常核型100例,检出率为30.12％.在141例社会性别为男性的DSD患者...     

急性一氧化碳中毒迟发性脑病继发性癫痫、心肌损害1例临床分析

报道1例急性一氧化碳中毒迟发性脑病继发性癫痫、心肌损害患者的临床表现、诊断及治疗经过,分析探讨糖皮质激素在治疗急性一氧化碳中毒迟发性脑病的应用时机和作用,并提示一氧化碳中毒患者出现感染、继发性癫痫等加重机体缺氧因素时,应及时进行心肌酶、心电图检查,利于早期诊治心肌损害。     

脑卒中后癫痫临床治疗分析

目的探讨脑卒中与癫痫的关系。方法对2187例脑卒中患者进行回顾分析。结果脑卒中后癫痫发生率为4．48％,以部分性发作为主,皮质病灶较非皮质病灶易发生癫痫,抗癫痫药物疗效满意。结论癫痫发作是脑卒中患者的常见症状,也是60岁以上老人新发生癫痫的主要病因。     

From gene to disease; progressive myoclonus epilepsy of Unverricht-Lundborg and mutations in the cystatin B gene

Progressive myoclonus epilepsy type 1 of Unverricht-Lundborg (EPM1) is a rare disorder, associated with mutations in the cystatin B (CSTB) gene. The most prevalent molecular abnormality is an expansion of a dodecamer repeat in the promoter region of the CSTB gene, but point mutations in the CSTB gene have also been found. DNA examination may be useful in discriminating EPM1 from juvenile myoclonic epilepsy, and from other types of progressive myoclonus epilepsy. An early diagnosis is important to optimise treatment and to provide an adequate prognosis and prediction of recurrence.     

小儿颅脑外伤后癫痫临床分析

目的 探讨颅脑外伤后继发癫痫患儿的危险因素.方法 通过门诊随访和辅助检查,对患儿的年龄、发作类型、神经体征、颅脑损伤程度、颅内并发症程度等进行分析和评价.结果 本组颅脑外伤发生年龄小于5岁者24例(66.67%),其中伤后1年内发病者18例;大于5岁发病者12例(33.33%),其中伤后1年内和5年以上发病者各6例.36例中呈全身性发作10例,部分或继发全身大发作分别为12例和14例;伴癫痫持续状态10例,伴口咽症7例.结论 外伤性小儿癫痫可发生于各年龄期.其主要危险因素包括:昏迷>12h的严重脑外伤、早期惊厥反复发作、局灶性神经征等;主要表现为部分或继发全身大发作;脑电图具有早期诊断及预后判断价值.     

妊娠合并癫痫32例临床分析

目的:了解妊娠与癫痫的相互影响以及孕期应用抗癫痫药物(AEDs)对胎儿的影响。方法:回顾性分析32例妊娠合并癫痫的孕妇癫痫发作时间、孕期服用AEDs情况、分娩方式和新生儿转归。结果:32例患者中,既往有癫痫病史26例,妊娠性癫痫患者6例;23例应用不同药物控制癫痫,9例孕期未服用AEDs;剖宫产26例,顺产6例;1例孕期未服药者的新生儿为唇裂畸形,余均为正常活婴。结论:孕期服用AEDs可能导致新生儿畸形,但由于频繁的强直-阵挛发作对母儿造成的危害比AEDs的致畸性更为严重,因此对未能有效控制痫性发作的孕妇孕期仍应规律服药。     

Multivariate analysis of complex gene expression and clinical phenotypes with genetic marker data

This paper summarizes contributions to group 12 of the 15th Genetic Analysis Workshop. The papers in this group focused on multivariate methods and applications for the analysis of molecular data including genotypic data as well as gene expression microarray measurements and clinical phenotypes. A range of multivariate techniques have been employed to extract signals from the multi-feature data sets that were provided by the workshop organizers. The methods included data reduction techniques such as principal component analysis and cluster analysis; latent variable models including structural equations and item response modeling; joint multivariate modeling techniques as well as multivariate visualization tools. This summary paper categorizes and discusses individual contributions with regard to multiple classifications of multivariate methods. Given the wide variety in the data considered, the objectives of the analysis and the methods applied, direct comparison of the results of the various papers is difficult. However, the group was able to make many interesting comparisons and parallels between the various approaches. In summary, there was a consensus among authors in group 12 that the genetic research community should continue to draw experiences from other fields such as statistics, econometrics, chemometrics, computer science and linear systems theory.     

Linkage analysis of low-density lipoprotein subclass phenotypes and the apolipoprotein B gene.

A common heritable phenotype has recently been identified which is characterized by a relative abundance of small, dense low-density lipoproteins (LDL), and mild elevations of plasma triglycerides and reductions in plasma high-density lipoproteins (HDL) cholesterol. This phenotype, designated LDL subclass phenotype B, has been associated with up to a three-fold increase in coronary disease risk. Complex segregation analysis in two large family studies has demonstrated that LDL subclass phenotype B is influenced by an allele at a single genetic locus with a population frequency of 0.25-0.3, and autosomal dominant inheritance, but with full penetrance only in males age 20 and over and in postmenopausal women. Since apolipoprotein B (apoB) is the principal protein component of LDL, linkage analysis was used to investigate possible linkage between the phenotype B phenotype and the apoB gene, using a variable number of tandem repeats site located 0.5 kb from the 3' end of the apoB gene. In 6 informative families including only family members in the penetrant classes, a total LOD score of -7.49 was found at a recombination fraction of 0.001. Thus, under the assumptions of the single gene model, it is unlikely that the apoB locus controls LDL subclass phenotype B.     

脑血管病后继发性癫痫临床特点及影像学分析

目的分析脑血管病后继发性癫痫的发生率及临床特点。方法将96例脑血管病后继发性癫痫的发生时间,表现形式,影像学检查特点进行统计研究。结果本组继发性癫痫发生率为12.8％,脑血管病后2周内发生癫痫者多于2周以上者,差异有显著性（P〈0.01）。结论继发性癫痫是脑血管病后并发症之一,会影响脑神经功能恢复,及时诊断及有效治疗有重要意义。     

大面积脑梗塞合并癫痫临床分析

探讨大面积脑梗死合并癫痫的临床特点。方法：回顾性分析39例大面积梗死患者的临床资料,其中9例大面积脑梗死合并癫痫。结果：大面积脑梗死合并癫痫发作率为23.07%,早发性癫痫占总发病数7.69%,迟发性癫痫占总发病数15.38%。结论：大面积脑梗塞更容易并发癫痫,积极抗癫痫治疗降低病死率。     

乳腺癌中BRCA1基因突变与雌激素受体的关系

目的探讨遗传性乳腺癌与卵巢癌易感基因(Hereditarybreastandovariancancersusceptibilitygene,BRCA1)基因突变、雌激素受体(Estrogenreceptor,ER)在乳腺癌中的作用以及二者之间的关系。方法选取64例乳腺癌患者标本作研究组,另取10例非癌乳腺组织标本作对照组。利用PCR-SSCP法和直接测序法检测BRCA1基因突变情况;利用SP(链霉菌抗生物素蛋白-过氧化物酶链接法)二步法检测ER,比较ER阳性组与ER阴性组BRCA1突变情况。结果10例非乳腺癌组织未检测出BRCA1基因突变。64例乳腺癌标本中检出BRCA1基因突变6例,突变率为9.4%。突变发生在5、12、17外显子上,均为错义突变,ER阳性44例,阳性率为68.75%(44/64)。ER阳性组中只有1例BRCA1突变(1/44),ER阴性组中有5例检出BRCA1突变(5/20),两组比较BRCA1突变率有显著差异性(P>0.05)。结论广西乳腺癌与BRCA1基因突变有关,BRCA1突变与雌激素受体有关,BRCA1基因突变病人雌激素阴性状态比非BRCA1基因突变病人多。     

广州市地区7234例新生儿耳聋基因突变分析

目的分析广州地区7 234例新生儿4个常见遗传性耳聋基因热点突变情况,为广州地区遗传性耳聋的防治提供依据。方法收集广州市天河区中山大学附属第三医院2015年6月至2019年1月分娩的7 234例新生儿脐带血液标本进行耳聋基因热点检测,基因突变新生儿行Sanger测序验证及基因外显子测序。结果检测到耳聋基因突变携带者266例(3.68%),其中GJB2基因突变159例(22.0%),SLC26A4基因突变85例(1.18%)。在266例的基因携带者中,GJB2 c.235delC杂合突变占49.6%(132/266),SLC26A4 IVS7-2A>G突变占28.2%(75/266),其余位点占22.2%。携带者一代测序验证结果与耳聋基因筛查结果一致,基因外显子测序中发现有3名双重突变患儿,两例为GJB2 c.235 del C与GJB2 c.109G>A双重杂合突变患儿,另一例为SLC26A4 IVS 7-2 A>G与SLC26A4 c.1983C>A双重杂合突变患儿,3例患儿经父母血液标本验证,双重杂合位点分别遗传自父母。结论本研究7 234例新生儿聋基因筛查中,GJB2基因突变频率最高,其次是SLC26A4基因,为耳聋儿童的早期发现与早期干预提供参考与指导。现行热点突变检测位点可能漏检其他突变位点,可根据本地检测情况调整或者制定适合本地的筛查方案。     

Subset testing and analysis of multiple phenotypes

Meta-analysis of multiple genome-wide association studies (GWAS) is effective for detecting single- or multimarker associations with complex traits. We develop a flexible procedure (subset testing and analysis of multiple phenotypes [STAMP]) based on mixture models to perform a region-based meta-analysis of different phenotypes using data from different GWAS and identify subsets of associated phenotypes. Our model framework helps distinguish true associations from between-study heterogeneity. As a measure of association, we compute for each phenotype the posterior probability that the genetic region under investigation is truly associated. Extensive simulations show that STAMP is more powerful than standard approaches for meta-analyses when the proportion of truly associated outcomes is between 25% and 50%. For other settings, the power of STAMP is similar to that of existing methods. We illustrate our method on two examples, the association of a region on chromosome 9p21 with the risk of 14 cancers, and the associations of expression of quantitative trait loci from two genetic regions with their cis-single-nucleotide polymorphisms measured in 17 tissue types using data from The Cancer Genome Atlas.