以免疫球蛋白和T细胞受体基因重排为标志定量检测MLL基因重排儿童急性淋巴细胞白血病的微小残留病和预后关系

目的 探讨MLL基因重排儿童急性淋巴细胞白血病（ALL）微小残留病（MRD）与临床特征的关系及其对预后的指导作用。方法 以2003年4月至2009年12月首都医科大学附属北京儿童医院血液肿瘤中心收治的MLL基因重排的ALL患儿为研究对象。以免疫球蛋白和T细胞受体基因重排、MLL融合转录本为标志,定量PCR方法监测MRD水平。以诱导治疗结束时MRD水平≥10-4为MRD阳性组,<10-4为MRD阴性组。卡方检验和Kaplan-Meier生存分析分别比较MRD阳性和阴性组临床特征和无事件生存率（EFS）的差异。结果 14例ALL患儿在诱导治疗结束时检测了MRD水平,MRD阳性组患儿初诊时外周血WBC计数显著高于MRD阴性组,对泼尼松实验治疗反应显著低于MRD阴性组。MRD阴性组5年EFS显著优于MRD阳性组,100% vs （37.5±17.1）%,P=0.022。结论 诱导治疗结束时MRD水平有助于对MLL基因重排儿童ALL进行预后分组,指导个体化治疗、改善预后。     

人类基因组印迹的研究进展及其意义

一、印迹现象的发现Hungtington舞蹈病是一种按常染色体显性遗传方式遗传的致残性神经系统疾病。发病的平均年龄为40岁，但发病年龄差异甚大，最小在4岁，最大在65岁。多在5～20年内死亡。在对该病做流行病学调查时发现，一部分患者的发病年龄和严重程度与他们受累双亲的性别相关。20岁前发病的病例多是从父亲遗传而来，而多数晚发病例则传自他们的母亲且病情较轻。研究表明这种情形并不能从母亲因素，如细胞质遗传、X一连锁和宫内因子找到解释，似乎有关遗传物质在通过父母传递时被印上了“较好”和“较不好”的烙印[1]。另一个例子是15号…     

人类附红细胞体病1例报告

附红细胞体病是一种人畜共患病,但人患此病的报道不多见,因此人患该病临床表现、病程、诊断、治疗方法及疗程尚无定论,现报道1例如下。     

比较基因组杂交技术及其在医学遗传学中的应用

比较基因组杂交（comparative genomic hybridization．CGH）是1992年Kallioniemi创立的基于荧光标记和分子、细胞遗传学技术鉴定基因组DNA的获得、丢失和扩增,并且可以把这些遗传变异定位在正常的中期染色体上的一种技术,也称之为中期CGH（metaphase—CGH）。主要特点是在一个实验中,用1张中期染色体涂片（metaphage spreads）,就能在全基因组范围内分析大的DNA拷贝数的不平衡改变,检测和定位DNA序列拷贝数的获得和丢失,即基因剂量的变化而不需要分裂的细胞。在其创立初期主要应用于肿瘤基因组学的研究。近年来,随着分子生物学技术的进步,经典的中期-CGH技术也有了很大的发展,在了解人类基因组的组织结构、基因定位和遗传病的诊断等方面发挥着越来越重要的作用。     

天津地区汉族Graves病患儿人类白细胞抗原-DQB1基因多态性

目的 检测天津地区汉族儿童Graves病(GD)人群的人类白细胞抗原(HLA)-DQB1基因,分析其易感基因,并观察家族性GD与散发性GD之间HLA-DQB1基因的差异.方法 采用PCR-序列特异性引物方法检测天津地区40例汉族GD患儿及50例健康儿童HLA-DQB1基因型,计算和比较各组间等位基因出现频率,并应用SPSS 11.5软件进行统计学分析.结果 1.GD组HLA-DQB1*0303基因分布频率与健康对照组比较明显增高(χ2=9.097,P=0.003);2.家族性GD组HLA-DQB1*0301基因频率分布与散发性GD组比较明显升高(χ2=9.724,P=0.002);3.DQB1*02、DQB1*0302等位基因频率比较差异均无统计学意义(P=0.953,0.414,0.902).结论 DQB1*0303基因是天津地区汉族儿童GD的易感基因,具有此基因者易患GD,而有GD家族史的儿童具有DQB1*0301基因也易患GD.     

2009-2010年苏州地区儿童重症人类博卡病毒肺炎的流行病学及临床特点

目的 了解人类博卡病毒(HBoV)感染所致儿童重症肺炎的流行病学及临床特点.方法 对2009年1月- 2010年12月本院PICU 27例重症HBoV肺炎患儿和106例重症RSV肺炎患儿的流行病学和临床特点进行比较分析.结果 重症HBoV肺炎患儿年龄(1.26±0.58)岁,显著大于重症RSV肺炎患儿[(0.49±0.57)岁](P＜0.05).重症HBoV肺炎患儿秋冬季发病占全年的66.7％(18/27例),与重症RSV肺炎患儿的88.7％(94/106例)比较差异无统计学意义;重症HBoV组66.7％(18/27例)的患儿有发热,高于重症RSV肺炎患儿的36.8％(39/106例);40.7％ (11/27)重症HBoV肺炎患儿有喘息,低于重症RSV肺炎患儿的92.5％(98/106例).100％(27/27例)重症HBoV肺炎患儿伴有咳嗽,11.1％(3/27例)伴有腹泻,无抽搐和胃肠道出血发生,66.7％(18/27例)患儿入院时氧合指数低于300 mmHg(1 mmHg =0.133 kPa),14.8％(4/27例)予机械通气,通气时间为(3.93±1.56)d,但无急性呼吸窘迫综合征(ARDS)发生,无死亡病例;48.1％(13/27例)患儿CK-MB升高,7.4％(2/27例)患儿肌钙蛋白(cTnI)升高,14.8％(4/27例)患儿AST、ALT升高,44.4％(12/27例)患儿CRP升高;影像学检查77.8％(21/27例)患儿双肺受累,63.0％( 17/27例)表现为肺门周围纹理粗重,88.9％(24/27例)表现为肺气肿,55.6％(15/27例)有小斑片影,14.8％(4/27例)有大范围病灶,14.8％(4/27例)出现肺不张,未出现胸腔积液和肺气漏征象.结论 苏州地区重症HBoV肺炎多见于2岁以下患儿,秋冬季为发病高峰,以发热、咳嗽、喘息和呼吸困难为主要表现,可出现低氧血症,但无ARDS发生,影像学表现以肺气肿和两肺门周围纹理改变为主,较少出现胸腔积液和肺气漏征象.     

重症人类博卡病毒肺炎住院患儿混合感染的临床研究北大核心CSCD

目的了解重症肺炎患儿中人类博卡病毒(hBoV)的感染情况,并探讨混合感染因素对疾病严重程度的影响。方法选取2012年1月至2015年12月苏州大学附属儿童医院呼吸科收治的335例重症肺炎患儿。入院时采集鼻咽分泌物行多病原学检查,采集外周血行血常规、C反应蛋白(CRP)及细胞免疫检测。结果335例重症肺炎患儿中共检出hBoV感染29例(8.6%),其中hBoV单纯感染22例(75.9%),混合其他病原感染者7例(24.1%),以hBoV混合肺炎支原体(MP)感染最为常见(4例,占57.1%)。混合感染组患儿年龄小于单纯感染者[7.0(5.0~12.0)个月比12.0(8.8~15.5)个月],差异有统计学意义(Z=2.174,P<0.05);混合感染组患儿发热的比例明显高于单纯感染组(57.1%比13.4%),差异有统计学意义(P<0.05);而在咳嗽、喘息、呼吸困难、发绀、肺部啰音、并发症发生率、hBoV载量方面2组比较差异均无统计学意义(均P>0.05)。混合感染组血常规白细胞总数高于单纯感染组[10.29(6.48~14.71)×10^9/L比13.77(9.41~18.11)×10^9/L],差异有统计学意义(Z=4.961,P<0.001)。2组入儿科重症监护室(PICU)的比例(57.1%比36.4%)比较,差异无统计学意义(P>0.05);但混合感染组PICU住院时间[3.0(3.0~3.0)d比1.0(1.0~1.0)d]和平均住院日[16.0(10.0~18.0)d比8.0(7.0~10.0)d]均明显长于单纯感染组,差异均有统计学意义(Z=9.034、14.818,均P<0.001)。结论hBoV是引起儿童重症肺炎的重要病原之一,单纯hBoV感染可引起重症表现,hBoV混合其他病原感染后在一定程度上会加重病情,但混合感染与病毒载量之间无显著相关性。     

婴儿急性白血病HRX基因重排及其意义

为探讨婴儿急性白血病细胞遗传学和分子生物学特征，采用ｈｕｔｈｅｒｎｂｌｏｔ（ＤＮＡ印迹）方法，用Ｒ／Ｓ４探针作分子杂交，在１２例＜２４个月的婴儿急性白血病（ＩＡＬ）中检测出７例有ＨＲＸ（同源于果蝇三胸基因）基因的重排，染色体１１ｑ２３上几乎所有的断裂点都集中在ＨＲＸ基因上一个狭窄的区域内。＜１８个月的７例ＩＡＬ中，有５例异常。结果提示，这种ＩＡＬ肿瘤细胞负荷大，预后差。     

IgH和TCR基因重排中寡克隆及克隆演化在MRD检测中的意义

近年来应用免疫球蛋白重链（ＩｇＨ）和（或）Ｔ细胞受体（ＴＣＲｓ）基因重排作为急性白血病细胞特异性标记,并作为白血病微小残留病（ｍｉｎｉｍａｌｒｅｓｉｄｕａｌｄｉｓｅａｓｅ,ＭＲＤ）的检测指标已有不少报道。应用分子杂交、ＰＣＲ等方法检测急性淋巴细胞白血病的ＩｇＨ和（或）ＴＣＲｓ基因重排,其阳性率分别为８０％～９５％和５０％～７０％［１,２］。但是在未检出ＩｇＨ和（或）ＴＣＲｓ基因重排的病例以及ＭＲＤ检测阴性的病例中,由于种种原因出现了假阴性,其中ＩｇＨ和（或）ＴＣＲｓ基因重排时寡克隆的形成及克隆演…     

47例儿童急性淋巴细胞白血病IgH和TCR基因重排

目的 检测４７例儿童急性淋巴细胞白血病（ＡＬＬ）ＩｇＨ和ＴＣＲ基因重排，以便选择恰当的组合用于微小残留病（ＭＲＤ）的检测。方法 以Ｃｈｅｌｅｘ１００为介质，从初诊的ＡＬ患儿骨髓涂片中提取ＤＮＡ，借助聚合酶链反应（ＰＣＲ）技术检测ＩｇＨ、ＴＣＲβ、ＴＣＲδ和ＴＣＲγ基因重排。结果 在Ｂ－ＡＬＬ（４２例）中，ＩｇＨ、ＴＣＲβ、ＴＣＲδ和ＴＣＲγ基因重排的检出结果分别为３２／４２例、１５／４２例、１９／     

Genomic imprinting and Wilms' tumor

The selective loss of maternal and reduplication of paternal chromosome 11p15.5 alleles in Wilms' tumors (WTs) points to the existence of a paternally imprinted tumor suppressor gene(s) and/or a maternally imprinted dose-dependent growth-promoting gene(s) in this chromosomal region. Two reciprocally imprinted chromosome 11p15.5 genes, H19, a candidate tumor suppressor gene, and IGF2, a candidate dominant oncogene, have been well-characterized in terms of their imprinting and expression status in WTs. Here we review and extend data indicating that a majority of WTs show a bipaternal epigenotype at these loci, with H19 inactive and IGF2 biallelically active. This can arise either through loss of heterozygosity (LOH) or by a non-LOH pathway involving localized biallelic hypermethylation of H19DNA. Conversion to this bipaternal endpoint has recently been found to affect not only these two genes, but also at least one other imprinted 11p15.5 gene, KIP2. Since 11p15.5 LOH and biallelic H19 hypermethylation can occur both early and late in tumor progression and since early loss is not associated with bilaterality or multifocality of WTs, these types of lesions appear to be permissive rather than rate-limiting in Wilms' tumorigenesis. © 1996 Wiley-Liss, Inc.     

Comparative genomic hybridization in pediatric acute lymphoblastic leukemia

Comparative genomic hybridization (CGH) was used to clarify the chromosomal status of 15 patients diagnosed with childhood acute lymphoblastic leukemia (ALL). Bone marrow samples from 10 of the 15 patients were selected because no metaphases were obtained for cytogenetic analysis. Three patients with normal trypsin and giemsa banding (GTG) karyotypes were also studied by CGH to determine whether significant abnormalities might have been missed by banding analysis, and samples from an additional 2 patients with hyperdiploidy were also included. Seven of the 10 patients with failed GTG banding analysis were found to be chromosomally abnormal by CGH; 2 out of 3 patients with normal GTG band karyotypes were abnormal, indicating that the metaphases available for karyotyping were not malignant cells, and that CGH analysis of hyperdiploid samples provided more accurate resolution than karyotyping alone. The prognostic value of chromosomal aberrations detected by CGH and the efficiency of the technique suggest a central role for CGH in routine clinical cytogenetics.     

DNA methylation errors in imprinting disorders and assisted reproductive technology

There have been increased incident reports of rare imprinting disorders associated with assisted reproductive technology (ART). ART is an important treatment for infertile people of reproductive age and is increasingly common. The identification of epigenetic changes at imprinted loci in ART infants has led to the suggestion that the techniques themselves may predispose embryos to acquisition of imprinting errors and disease. It is still unknown, however, at what point(s) these imprinting errors arise, or the risk factors. In this review it was hypothesized that the particular steps of the ART process may be prone to induction of imprinting methylation errors during gametogenesis, fertilization and early embryonic development. In addition, imprinting diseases and their causes are explained. Moreover, using a Japanese nationwide epidemiological study of imprinting diseases, their association with ART is determined. Epigenetic studies are required to understand the pathogenesis of this association; the ART‐related risk factor(s); and the precautions that can be taken to prevent the occurrence of these syndromes. It is hoped that the constitution of children born after ART will indicate the safest and most ethical approach to use, which will be invaluable for the future development of standard ART treatment.     

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??The clinical manifestations of neurodevelopmental disorders in children are varied?? though co-occurring sleep disorders in the population is very common. The incidence?? severity?? course?? treatment difficulty and recurrence rate are also significantly higher than those of typically developing children. In addition?? sleep disorders result in more significant impairment in children with neurodevelopmental disorders in terms of cognition?? emotion?? behavior and social development?? and even negatively affect the family sleep quality and quality of life. However?? pediatric clinicians have been lacking knowledge of sleep disorders?? as well as the capability of assessment and treatment. Therefore?? begin with the etiology and risk factors of sleep disorders in children with neurodevelopmental disorders?? the clinical symptoms and the methods of assessment and intervention are introduced to help pediatric clinicians to enhance the diagnosis and treatment of sleep disorders in the children with neurodevelopmental disorders?? and improve the children’s daytime function?? rehabilitation efficacy and family sleep quality and quality of life through promoting sleep.     

四例Prader-Willi综合征患儿的分子遗传缺陷分析

目的 观察Pradet-Willi综合征(PWS)患者的分子遗传基础及临床筛查策略,为进一步的遗传咨询提供信息。方法 应用甲基化特异性PCR(MSPCR)及荧光原位杂交(FISH)技术对4例临床诊断PWS患者进行基因分析研究。结果 4例患者MSPCR结果均显示缺乏父源的相关片段,而仅为母源DNA,即第15号染色体母源单亲二体(matUPD15);FISH检测发现2例15q近端SNRPN基因片段的微小缺失。结论 父源15q11-13特异区带缺失及matUPD15亦与我国PWS患者致病的分子病理缺陷有关。临床开展相关的细胞分子遗传学实验诊断对PWS临床诊断及遗传咨询、产前诊断都具有积极的作用。     

先天性糖蛋白糖基化缺陷导致的疾病

先天性糖蛋白糖基化缺陷(congenital disordersof glycosylation,CDG)是一组由常染色体隐性遗传引起的糖蛋白合成缺陷而导致的疾病,可引起一系列临床表现[1]。糖蛋白的蛋白糖基化修饰是一个极其复杂的过程,参与其中的酶种类繁多。糖蛋白糖基化缺陷可累及多个脏器,如神经、造血、消化和生殖系统等,从而引起多种多样的临床表现。该病最早由比利时儿科医师Jaeken等[2]于1980年首次报道。迄今根据缺陷的酶、缺陷部位已报道有19型,见表1。1CDG的分型糖蛋白由糖链和多肽链组成,其糖链又有O!糖苷键连接的糖链和N!糖苷键连接的糖链2种。CDG患者…     

婴幼儿巨细胞病毒感染对红细胞系统造血功能的影响

目的 探讨人巨细胞病毒感染对婴幼儿红细胞系统(简称红系)造血功能的影响.方法 对2007年1至10月收治于我院儿科血液病房的21例伴有红系改变的巨细胞病毒感染婴幼儿的临床资料进行回顾性分析.结果 巨细胞病毒感染的婴幼儿可发生红系造血改变如贫血、急性溶血、急性造血功能停滞、急性白血病、噬血细胞综合征、传染性单核细胞增多综合征等多种疾病.结论 婴幼儿巨细胞病毒感染能通过多系统多靶位影响红系造血,增加红系破坏,甚至造成骨髓恶性增殖性疾病,应受到高度重视.     

Autistic spectrum disorders

Autistic spectrum disorders is a complex developmental disorder with social and communication dysfunction at its core. It has a wide clinical spectrum with a common triad of impairments — social communication, social interaction and social imagination. Even mild or subtle difficulties can have a profound and devastating impact on the child. To be able to provide suitable treatments and interventions the distinctive way of thinking and learning of autistic children has to be understood. The core areas of social, emotional, communication and language deficits have to be addressed at all levels of functioning. The important goals of assessment include a categorical diagnosis of autism that looks at differential diagnosis, a refined precise documentation of the child’s functioning in various developmental domains and ascertaining presence of co-morbid conditions. The interventions have to be adapted to the individual’s chronological age, developmental phase and level of functioning. The strategies of curriculum delivery and teaching the child with autism is distinctive and includes presence of structure to increase predictability and strategies to reduce arousal of anxiety