发根脆性X智力低下蛋白检测法诊断脆性X综合征

目的：至今已有多种筛查和诊断脆性X综合征(fragile X syndrome,FXS)的方法,以PCR法和Southern印迹方法应用最广,然而每种方法均存在各自的局限性。该研究探讨发根脆性X智力低下蛋白（fragile X mental retardation protein,FMRP）检测在诊断或筛查FXS中的可靠性,以建立一种快速、简便、价廉且可靠的诊断FXS的方法。方法：采用发根FMRP免疫组化的检测方法对80例健康儿童、40例不明原因智力低下儿童、已确诊FXS家系成员12例进行检查; 用7-deza-dGTP PCR 法进行对照,探讨其对诊断FXS的应用价值。结果：在80例健康儿童中,发根FMRP的表达率均在80%以上。40例不明原因智力低下患儿中,2例确诊为FXS患儿的发根FMRP表达率分别为10%和0,另38例非FXS患者发根FMRP的表达率均在80%以上。在FXS家系调查中,确诊的2例FXS患者的发根FMRP表达率均为0。结论：发根FMRP检测诊断FXS具有快速、简便、价廉、可靠等特点,值得进一步推广应用。［中国当代儿科杂志,2009,11（10）：817-820］     

脆性X智力低下蛋白的研究进展

脆性X综合征是最常见的遗传性智力低下性疾病之一，临床表现及贵传方式都有其独特之处，研究发现，家族性智力低下蛋白的缺乏在本病的发病中起重要作用。本文从该蛋白的结构、分布、功能、与学习记忆的关系及其在诊断中的应用等几个方面进行综述。     

脆性X智力低下蛋白的研究进展

脆性Ｘ综合征是最常见的遗传性智力低下性疾病之一,临床表现及遗传方式都有其独特之处。研究发现,家族性智力低下蛋白的缺乏在本病的发病中起重要作用。本文从该蛋白的结构、分布、功能、与学习记忆的关系及其在诊断中的应用等几个方面进行综述。     

智力低下儿童颅骨X线检查

1981年卫生部组织调查队对柞水县14岁以下儿童进行智力筛查时,我们对部分智力低下(以下简称智低)儿童进行了头颅X线检查,现将结果报告如下。 临床资料     

脆性X综合征的临床及细胞遗传学研究：附两家系分析

应用FUdR及Caffein诱导方法检出两家族共8例脆性X综合征患者,4例携带者。指出,智力低下伴多动、大耳朵及不明原因的癫病发作是青春期前患者进行脆性X检查的临床指征。     

脆性X基因FMR-1的分子遗传研究

脆性Ｘ综合征是一种以智力障碍表现为主的Ｘ连锁遗传病,该病与位于Ｘｑ２７．３处的一个对叶酸敏感的脆性位点有关。我们用Ｓｏｕｔｈｅｒｎ印迹杂交及ＰＣＲ技术对脆性Ｘ相关基因ＦＭＲ１进行了基因分析,现报道如下。对象：用细胞遗传学方法从５５名男性智力低下患者...     

脆性X综合征的筛查、诊断和治疗

目的 为简化筛查标准，提高对脆性X综合征（FRAXA）筛查、诊断和治疗能力。方法 采用九条标准，智力低下、智力低下家族史、长脸、（或突出）耳朵、注意力不集中及多动、孤独行为、通贯掌、巨睾和关节过度伸展。对208例可疑FRAXA（男190例，女18例）的筛查进行回顾性分析。用PCR方法扩增（CGG）n三核苷酸重复序列作筛查，对PCR－Southern杂交作诊断；用叶酸及早期干预进行治疗。结果 用PCR－Southern杂交法诊断FRAXA7例。分析通贯掌、巨睾及关节过度伸展在FRAXA的筛查中出现的频率低，与诊断相关不甚密切，故采用简化的六项标准，如果评分≥6分，应作进一步检测；评分＜6分，60％以上的病例可以除外FRAXA，且不遗漏任何阳性病例。对6／7例用叶酸进行治疗，治疗有效，未发现副作用。结论 简化的六项标准明显提高了FRAXA的临床筛查的阳性率；而PCR方法快捷、简便，适用于FRAXA的筛查。叶酸治疗此综合征有效。     

脆性X综合征临床特征和基因诊断

脆性Ｘ综合征以不同程度智力低下、颅面部异常、巨睾为主要临床特征，染色体上Ｘｑ２７．３脆性位点的显示是细胞学上诊断脆性Ｘ综合征的重要指标。近年来，其分子机制的揭示为基因诊断提供了依据。本文着重对Ｆｒａ（Ｘ）临床特征、基因诊断及最新研究进展作一综述。     

脆性X综合征的筛查与诊断

脆性Ｘ综合征是引起先天性智力低下常见疾病,仅次于Ｄｏｗｎ综合征,由家族性智力低下基因（ＦＭＲ）－１动态突变引起,具有独特的遗传方式和临床表现,本文综述了疾病有关细胞遗传学,分子生物学和免疫细胞化学方面的筛查及诊断方法。     

GABAA受体与脆性X综合征

脆性X综合征(fragile X syndrome,FXS)是引起先天性智力低下的常见疾病,GABAA受体是哺乳动物中枢神经系统内最主要的抑制性神经递质受体,与焦虑、抑郁、癫癎、睡眠、认知等相关.多项研究证明GABA能神经系统特别是GABAA受体的变化与FXS的遗传表型有关.GABAA受体某些亚基的表达变化是FXS患者神经行为学改变的原因之一,可为FXS的治疗提供一个新的方向.     

Research in mental retardation: toward an etiologic approach

Over the past two decades, mental retardation research converges on three general themes: co-occurring mental retardation and psychopathology; families of offspring with mental retardation; and the developmental approach regarding behavioral sequences and profiles. Intertwined with each theme is a mounting body of research on genetic mental retardation syndromes. We first review recent progress in each of the three domains--psychopathology, families, and development--based on studies of groups with heterogenous or nonspecific mental retardation. We then show how new findings from specific genetic syndromes take this knowledge even further, as well as aid in the search for genetic, physiological, and environmental mechanisms associated with certain behaviors. We end the review by briefly summarizing our reasons for promoting an etiological approach to future mental retardation research, as well as by discussing methodological and other challenges.     

Behavioural and cognitive phenotypes in idiopathic autism versus autism associated with fragile X syndrome

Background:  In order to better understand the underlying biological mechanism/s involved in autism, it is important to investigate the cognitive and behavioural phenotypes associated with idiopathic autism (autism without a known cause) and comorbid autism (autism associated with known genetic/biological disorders such as fragile X syndrome). Parental effects associated with each type of autism also serve to cast light on the biological underpinnings of autism.
Method:  Forty-nine participants with idiopathic autism (AD; Mean age: 11.16; SD: 6.08) and their parents (45 mothers; 34 fathers), and 48 participants with fragile X syndrome and co-morbid autism (FXS/AD; Mean age: 17.30; SD: 10.22) and their parents (32 mothers; 30 fathers) were administered the ADOS-G and the age-appropriate Wechsler test to ascertain autism and cognitive profiles respectively.
Results:  The AD and FXS/AD groups showed a similar profile on the ADOS domains, with slightly higher scores on the Communication domain in the FXS/AD group, after adjusting for full-scale IQ. Marked differences between the groups in their cognitive abilities were apparent, with the FXS/AD group showing significantly lower scores on all subtests except Comprehension. While no parental effects were found for the FXS/AD group, a paternal effect was apparent on the combined ADOS score for the AD group. Moreover, midparental effects were found in this group for full-scale IQ (FSIQ) and verbal IQ (VIQ). Analyses also revealed parental effects for the subtests of Similarities, Vocabulary, and Information with predominantly maternal effect, and Digit Span with predominantly paternal effect. Both parents contributed to the midparental effect for Processing Speed.
Conclusions:  The results, together with our previous findings, suggest that the postulated combination of susceptibility genes for autism may primarily involve cognitive rather than behavioural processes.     

Cytogenetic Findings in Moderate and Severe Mental Retardation A Study of an Institutionalized Population of 1991 Patients

The cytogenetic data of a large scale study in an institutionalized population of 1991 moderately and severely mentally retarded patients are presented. In 21.3% of these patients a chromosomal aberration was diagnosed (14.9% Down syndrome patients and 3.5%"other chromosomal anomalies"). A fragile X screening was performed in 354 males, and was found to be positive in 57 (16.1% positive). Different chromosomal variants were present in another 6% of this population. Detailed results are presented on the different groups of chromosomal aberrations.     

Infantile Autism and the Fragile X Syndrome in Japanese Children

A total of 97 children with infantile autism, 85 boys and 12 girls, were screened for the fragile X chromosome. They ranged in age from 2 to 14 years with an average of 5 5/12 years. There were two fra(X) positive boys and no such girls. ( Acta Paediatr Jpn 1989; 31: 163 - 165)     

Syndromes and disorders associated with mental retardation

This article reviews selective comments on the concept of Mental Retardation (MR) in adolescents. Issues covered include the definition, prevalence, and differential diagnosis of MR. Some of the syndromes and disorders associated with MR in the adolescents are also considered with emphasis on the behavioral concerns that may be present in this age group. Finally, concepts of management by the clinician are reviewed. It is recommended that health care professionals caring for adolescents with MR should help these youths maximize their potential as human beings, helping them achieve meaningful functioning in adulthood.     

Fragile X syndrome among children with mental retardation

Prospective screening for fragile X syndrome was carried out among 1,111 patients with mental retardation who attended the Genetic clinic. Using defined clinical criteria, 55 patients were selected for cytogenetic studies to detect folate sensitive fragile sites. Twenty patients were diagnosed to have the fragile X syndrome. The prevalence of fragile X (A) syndrome was 18 per 1,000 patients of both sexes with mental retardation, 2.8% among male patients with mental retardation, and 5.8% among subjects with nonspecific mental retardation.     

孤独症儿童脆性位点精神发育迟滞1基因检测

目的对孤独症儿童进行脆性位点精神发育迟滞1(FMR-1)基因检测,探讨儿童孤独症与FMR-1基因的关系。方法孤独症患儿75例。用一般情况调查表进行调查,以儿童孤独症评定量表、孤独症行为检查量表筛查可疑患儿,按照中国精神障碍分类与诊断标准第3版(CCMD-3)的儿童孤独症诊断标准进行诊断和FMR-1基因检测。结果孤独症患儿FMR-1基因异常率极低,仅1.3%。结论儿童孤独症遗传学发病机制可能与FMR-1基因无关。     

Social behavior and cortisol reactivity in children with fragile X syndrome

OBJECTIVE: To examine the association between limbic-hypothalamic-pituitary-adrenal (L-HPA) axis reactivity and social behavior in children with fragile X syndrome (FXS). METHOD: Salivary cortisol changes and concurrent anxiety-related behaviors consistent with the behavioral phenotype of FXS were measured in 90 children with the fragile X full mutation and their 90 unaffected siblings during a social challenge task in the home. RESULTS: Boys and girls with FXS demonstrated more gaze aversion, task avoidance, behavioral signs of distress, and poorer vocal quality than the unaffected siblings. Multiple regression analyses showed that after accounting for effects of IQ, gender, age, quality of the home environment, and basal cortisol level, cortisol reactivity to the task was significantly associated with social gaze in children with FXS. The most gaze-aversive children with FXS had cortisol reductions, whereas those with more eye contact demonstrated the most cortisol reactivity. Unaffected siblings demonstrated an opposite pattern in which less eye contact was associated with increased cortisol reactivity. CONCLUSIONS: Results of the study suggest a unique relation between abnormal gaze behavior and L-HPA mediated stress reactivity in FXS.     

脆性X综合征患儿细胞内环磷酸腺苷降低的机制

目的 探讨脆性X综合征细胞内环磷酸腺苷(cAMP)降低的机制。方法 通过基因封闭方法，建立Fra(X)细胞模型，研究cAMP代谢途径中的两个关键酶腺苷酸环化酶(AC)及磷酸二酯酶(PDE)的活性变化。结果 试验组AC的比活力明显低于对照组(P＝0．000)，而PDE比活力则无显著改变(P＝0．983)。结论 Fra—(X)细胞内cAMP水平的降低可能与AC活性的抑制有关，而与PDE活性无明显关系。