儿童自闭症的遗传学研究进展

自闭症是一种以语言发育障碍、社会交往障碍及兴趣范围狭窄、行为刻板为主要特征的神经发育性疾病。通过同胞对和家系研究表明,其遗传度可高达90％。本文对近年来在自闭症遗传学研究方面的进展进行了论述,着重介绍目前的一些研究手段和分析方法,包括细胞遗传学、候选基因、连锁分析、拷贝数变异以及全基因组关联分析等研究。     

眼动技术对自闭症患者认知行为学研究的可视化分析

背景:眼动技术因其能客观及时且无创地反映自闭症患者的眼球运动和注意特征,较好地弥补了传统测量方法缺乏的客观性,得到了中国学者的关注,目前尚无针对眼动技术研究自闭症患者的可视化分析.目的:利用文献计量学方法对自闭症眼动研究的相关中英文文献进行可视化分析,了解中国和国际上该领域的研究概况、热点及趋势.方法:检索Web of...     

基因组分析证实免疫系统导致自闭症

据Saxena V 2012年12月4日[PLoS ONE,2012,7（12）：e48835]报道,在一项新的研究中,研究人员利用鉴定出促进自闭症产生的基因的新方法而发现证据证实几种与免疫系统相关联的途径遭受扰乱后促进自闭症谱系障碍产生。通过整合与自闭症相关联的DNA序列变异分析和在研究受到自闭症影响的家庭中鉴定出的标志物分析,这项研究强有力地表明免疫功能在自闭症中发挥着作用。     

一例Helsmoortel-van der Aa综合征患儿的 ADNP基因变异分析

目的:探讨l例特殊面容、智力低下、语言发育迟缓和自闭症谱系障碍患者的分子遗传学病因。方法:抽提患者及其家系成员外周血基因组DNA,应用二代测序技术对患者外显子组基因序列进行检测,Sanger测序验证家系可疑致病位点,依据美国医学遗传学与基因组学学会指南对疑似致病性变异位点进行分析。结果:全外显子测序提示患者 ...     

基因突变可增加儿童患自闭症的几率

当科学家们逐步揭示自闭症原因时，这种复杂的发育性疾病也迅速地显示它的多种根源，让我们审视一下2个新的遗传学研究。     

人类与医学遗传学群体与家系资料分析计算机系统：连锁分析

本文简介我们用C语言编制的人类与医学遗传学群体与家系资料分析计算机系统中的连锁分析的功能,包括常染色体位点连锁分析、X染色体位点连锁分析、常染色体连锁异质性分析.对人类与医学遗传学及遗传流行病学研究都很有实用价值.     

神经发育障碍伴或不伴自闭症特征和(或)脑结构异常患儿1例的 NOVA2基因变异分析

目的探讨1例神经发育障碍伴或不伴自闭症特征和(或)脑结构异常患儿的遗传学病因。方法选取2021年7月至郑州大学第三附属医院就诊的1例NEDASB患儿为研究对象。抽取患儿及其父母的外周血样, 采用高通量测序技术对患儿进行基因检测, 对候选变异进行Sanger测序验证以及生物信息学分析。结果基因检测结果显示患儿携带NOVA2基因c.820₈28delinsCTTCA(p.Thr274Leufs*121)杂合变异。其父母均未携带相同的变异。根据美国医学遗传学与基因组学学会相关指南, 判断其为致病变异。结论 NOVA2基因c.820₈28delinsCTTCA(p.Thr274Leufs*121)杂合变异可能是本例患儿的遗传学病因。上述发现丰富了NOVA2基因的变异谱, 为遗传咨询及产前诊断提供了依据。     

自闭症患者记忆损伤的研究进展

近年来,自闭症的发生几率逐渐上升,针对自闭症的研究也在逐步增加.但是,关于自闭症患者记忆下降的研究,尤其是其相关因素以及如何提高自闭症患者记忆力方面的研究尚存不足.现有的相关文献尚无明确有效改善自闭症患者记忆力的方法.本文主要综合讨论了自闭症患者记忆下降神经心理学因素及不同的治疗方法,并展望其未来研究可能的方向.     

一例常染色体显性遗传性智力障碍7型患儿的临床和遗传学分析

目的:对1例临床表现为全面发育落后、癫痫、异常面容的患儿进行临床和遗传学分析。方法:收集患儿临床资料,抽取患儿及父母外周血,应用高通量捕获测序分析,对可疑致病变异进行Sanger测序验证及生物信息学分析。结果:患儿临床表现为全面发育落后、癫痫发作、自闭症、特殊面容,高通量测序结果显示 DYRK1A基因第11...     

一个染色体14q微缺失的遗传学分析

目的分析1例自闭症、智力低下和癫痫患儿的遗传学病因。方法应用常规G显带染色体核型分析、单核昔酸多态性微阵列(single nucleotide polymorphism array,SNP array)技术检测染色体变异,用高通量测序筛选致病变异位点,Sanger测序验证,查阅数据库及文献分析,以明确缺失区及致病变异基因的病理意义。结果患儿及其父母外周血G显带核型分析结果均未见异常。SNP array检测发现患儿染色体14 qll.2区存在460 kb的缺失,高通量及Sanger测序显示患儿携带NALCN基因新发变异,患儿及其母亲COL4A5基因发生半合子变异。结论染色体14qll.2微缺失与NALCN变异可能与患儿自闭症、智力低下及癫痫等表型相关。     

孤独症儿童睡眠障碍对照研究

目的比较孤独症儿童与正常儿童睡眠障碍发生情况。方法对140例确诊的孤独症儿童和82例正常儿童,用自编睡眠及一般情况问卷进行调查。结果在140名孤独症儿童中,共有102名儿童目前或既往存在睡眠障碍,其中,男孩85人,女孩17人,孤独症儿童睡眠障碍的终生患病率为72.86%,男孩终生患病率(72.03%)和女孩终生患病率(77.27%)差异无统计学意义(χ2=1.912,P=0.384)。在82名正常儿童中,共有14名儿童目前或既往存在睡眠障碍,其中,男孩10人,女孩4人,正常儿童睡眠障碍的终生患病率为17.07%,男孩终生患病率(16.67%)和女孩终生患病率(18.19%)差异无统计学意义(χ2=0.080,P=0.117)。孤独症儿童的睡眠障碍发病率明显高于正常儿童,差异无统计学意义(χ2=32.407,P=0.000)。结论孤独症儿童睡眠障碍发生多于正常儿童,睡眠障碍是孤独症儿童主要症状之一。     

Association studies of the CT repeat polymorphism in the 5′ upstream region of the cholecystokinin B receptor gene with panic disorder and schizophrenia in Japanese subjects

The tetrapeptide of cholecystokinin (CCK), CCK‐4, is known to induce panic attacks in human subjects, while CCK‐8 is reported to have a therapeutic effect on schizophrenia symptoms. Recently, we have identified a novel microsatellite polymorphism in the 5′ upstream region of the CCK gene and shown a significant association between this polymorphism and panic disorder. In this study, we have investigated the CCK‐B receptor (CCKBR) gene, which is the main constituent of the CCK receptor in the CNS. Recently, a dinucleotide repeat, (CT)_n, in the 5′ regulatory region of the CCKBR gene was reported to be associated with panic disorder in Canadian samples. To evaluate an association of the CT repeat with panic disorder and schizophrenia, we genotyped 71 subjects with panic disorder, 154 schizophrenics and 199 controls. However, no evidence of allelic association was found between the polymorphic repeat of the CCKBR gene and either panic disorder or schizophrenia (P = 0.186 and 0.987, respectively). Together with the negative reports on association analyses using other polymorphisms of the CCKBR gene and Japanese samples, the present results exclude a major genetic contribution of the CCKBR gene to susceptibilities to panic disorder and schizophrenia in Japanese cohorts. © 2001 Wiley‐Liss, Inc.     

Association analysis of the functional Ala111Glu polymorphism of the glyoxalase I gene in panic disorder

The zinc metalloenzyme glyoxalase I (GLO1) is thought to play a role in anxiety disorders because a reduced brain expression of GLO1 has been associated with increased anxiety-behaviours in mice. Recently, a functional Ala111Glu polymorphism in GLO1 has been shown to result in a reduced enzyme activity. The present study tested the hypothesis that this common genetic variant could confer susceptibility to panic disorder using an Italian population sample of 162 panic disorder patients and 288 matched controls. Statistical analysis failed to show association with the overall diagnosis of the disease. However, a weak but significant association was demonstrated between this polymorphism and panic disorder without agoraphobia. While our data suggest that this polymorphism is unlikely to have a major function in the pathogenesis of panic disorder, it could play a role in the subgroup of patients without agoraphobic avoidance.     

Lack of association between bipolar affective disorder and tyrosine hydroxylase DNA marker

Sixty-eight patients with bipolar affective disorder and 88 controls were investigated for genetic association of tyrosine hydroxylase (TH) restriction fragment length polymorphisms (RFLPs). No significant association between bipolar affective disorder and TH was found. Thus the hypothesis that TH is involved in the pathogenesis of bipolar affective disorder was not supported. © 1993 Wiley-Liss, Inc.     

Treating comorbid depression and avoidant personality disorder: The case of Andy

Major depressive disorder is among the most frequently diagnosed mental disorders and is often accompanied by other disorders such as anxiety or substance abuse. As a result of a complicated tangle of comorbidities, psychotherapy in such cases can become quite demanding. The present case study presents and discusses the challenges represented by a complex case of psychotherapy, focusing on ongoing modifications of the clinical hypotheses and therapeutic approach. This process is illustrated through the case of Andy, a 44-year-old man suffering from depressive disorder, social phobia, substance dependency, and an avoidant personality disorder. This case draws attention to the quality of the relationship and the flexibility and adaptation required from the therapist while depicting an integrative way of working therapeutically with complex cases.     

Genetic examination of the Mood Disorder Questionnaire and its relationship with bipolar disorder

The Mood Disorder Questionnaire (MDQ) is a common screening tool for bipolar disorder that assesses manic symptoms. Its utility for genetic studies of mania or bipolar traits has not been fully examined. We psychometrically compared the MDQ to self-reported bipolar disorder in participants from the United Kingdom National Institute of Health and Care Research Mental Health BioResource. We conducted genome-wide association studies of manic symptom quantitative traits and symptom subgroups, derived from the MDQ items (N = 11,568–19,859). We calculated genetic correlations with bipolar disorder and other psychiatric and behavioral traits. The MDQ screener showed low positive predictive value (0.29) for self-reported bipolar disorder. Neither concurrent nor lifetime manic symptoms were genetically correlated with bipolar disorder. Lifetime manic symptoms had a highest genetic correlation (r_g = 1.0) with posttraumatic stress disorder although this was not confirmed by within-cohort phenotypic correlations (r_p = 0.41). Other significant genetic correlations included attention deficit hyperactivity disorder (r_g = 0.69), insomnia (r_g = 0.55), and major depressive disorder (r_g = 0.42). Our study adds to existing literature questioning the MDQ's validity and suggests it may capture symptoms of general distress or psychopathology, rather than hypomania/mania specifically, in at-risk populations.     

Tourette综合征的共病临床研究

目的：了解Tourette综合征共病的种类、发生率及相关因素。方法：以CCMD-3诊断标准为依据，分别采用耶鲁综合抽动严重程度量表(YGTSS)、Achenbach儿童行为量表(CBCL)、莱顿(Leyton)强迫量表、康纳(Conners)儿童行为问卷和家庭情况调查表，对125例Tourette综合征逐一进行评定。结果：Tourette综合征与注意缺陷多动障碍共病率为41．6％，与强迫症的共病率为25．6％，与焦虑障碍的共病率为8．0％，与抑郁障碍的共病率为4．8％，与品行障碍的共病率为8．0％，与自伤的共病率为3．2％，与睡眠障碍的共病率为2．4％。结论：Tourette综合征的共病种类多，患病率高，影响TS的治疗及预后。共病通常是TS儿童功能损害的来源，并增加疾病的复杂性和严重性，应该引起高度重视。     

Type I bipolar disorder associated with a fragile site on chromosome 1

The objective of this paper is to study the association between chromosomal fragile sites and type I bipolar disorder. This case-control study compares bipolar patients with normal controls. Ten cases of type I bipolar disorder diagnosed according to DSM-III-R criteria and the Composite International Diagnostic Interview (CIDI) were selected from the Escola Paulista affective disorders outpatient clinic and 10 healthy controls (CIDI negative for psychiatric diagnoses) matched for sex and age were drawn from the otorhinolaryngologic outpatient clinic of the same hospital. The cytogenetic analysis was carried out with blood lymphocytes, which were cultured in a folic acid--free medium. A total of 100 mitoses per subject were blindly analyzed to the psychiatric diagnostic assignment, and fragile sites were identified according to a minimum expected frequency of events per band in conformity with a Poisson distribution. A higher frequency of chromosomal lesions for cases than controls was found for the following bands: 1q32, 5q31, and 11q23, the 1q32 being considered a fragile site. Although no evident neuropsychiatric etiological component has been mapped to the 1q32 region so far, this finding may lead to further investigation of a possible linkage between genetic markers of this region and bipolar disorder. © 1995 Wiley-Liss, Inc.     

帕罗西汀合并认知行为疗法治疗强迫症的对照研究

目的评价帕罗西汀合并认知行为疗法对强迫症的治疗效果。方法将符合中国精神障碍分类与诊断标准第3版的57例强迫症患者随机分为治疗组和对照组,治疗组给予帕罗西汀合并认知行为治疗,对照组单用帕罗西汀治疗,应用临床疗效标准及耶鲁布朗强迫量表(Y—BOCS)定期评定;观察6个月。结果在治疗1、2、4个月和6个月时,治疗组疗效显著优于对照组,尤其对强迫行为疗效更好。结论帕罗西汀合并认知行为疗法联合治疗强迫症效果优于单用帕罗西汀治疗。