Objective: To investigate the clinical features of two autosomal dominant Parkinson's disease pedigrees and to identify the chromosomal locus where the pathogenic genes are located by genetic linkage analysis, so as to accumulate some experience for genetics research of Parkinson's disease pedigree. Methods: A total of 35 person from two pedigrees were studied. Incidence characteristics were studied from the pedigree members' medical history, physical examination, Parkinson's disease exercise and non-motor symptom scale determination, line related auxiliary examination. Genomic DNA was extracted from peripheral anticoagulation of the pedigree members, and chromosomal locus where the pedigree pathogenic genes were located was analyzed by two-point linkage technique. Results: Both pedigrees had typical clinical manifestations of Parkinson's disease and had characteristics of early onset and.similar clinical symptoms. Both were autosomal dominant Parkinson's disease pedigrees. Fluorescently labeled STR genetic markers were used for linkage analysis of four candidate gene loci of PARK1, PARK3, PARK5 and PARK8. The results showed that pathogenic gene of pedigree 1 had linkage to STR polymorphic locus D12S85 near 12 chromosome 12q12 locus, and had some distance of linkage with D1251668 (<10 cM). Relevant chromosomal linkage locus was not detected in pedigree 2. Conclusion: Pedigree 1 is autosomal dominant Parkinson's disease pedigree characterized by tremor and stiffness. Linkage analysis showed certain correlation between STR D12885 and D12S1668 locus of PARK8. Because LRRK2 is a PD -related gene near the two STR loci, we speculate that LRRK2 mutation may be the pathogenic gene of the pedigree. Also, the presence of another PD -related pathogenic gene near LRRK2 gene is possible. Pedigree 2 is autosomal dominant Parkinson's disease pedigree characterized by Stiffness. Genes linked to the four candidate loci were not detected. The first speculation is that pathogenic gene of the pedigree may be irrelevant with the above research locus; the second is that linkage analysis results are affected by the less pedigree members.

Introduction: Glucocerebrosidase (GBA) mutations and leucine-rich repeat kinase 2 (LRRK2) variants are the most common genetic risk factors for late-onset Parkinson's disease (PD). In this study, we aimed to investigate the differences in pre-diagnostic symptoms of PD associated with the variants. Methods: The participants were recruited from 24 centers across China and genotyped for LRRK2 G2385R and R1628P variants and GBA L444P mutation. Participants were surveyed with structural questionnaires for history of environmental exposure and living habits and interviewed to collect the time at onset of each symptoms before diagnosis. We compared the cumulative prevalence and manifestation pattern of symptoms between groups using multiple logistic regression, adjusting age and gender. Results: Total 1799 PD patients were recruited, including 226 patients with LRRK2 G2385R or R1628P variant, 44 with GBA L444P mutation, three with both LRRK2 and GBA mutation, and 1526 idiopathic patients. The cumulative prevalence of non-motor and typical motor symptoms did not differ between groups before diagnosis (P > 0.05). The manifestation sequences of non-motor symptoms were indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic PD subjects, and followed the sequence of constipation, hyposmia, sleep disorders, anxiety and depression, sexual dysfunction, urinary incontinency, dizziness and cognition. Slightly higher prevalence of hypomimia and micrographia were detected in the GBA-carriers. Conclusions: The prevalence of pre-diagnostic symptoms is almost indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic PD before diagnosis; the sequence of the manifestation of non-motor symptoms largely conforms to the Braak stage for both genetic-related and idiopathic late-onset PD.

Rapid and sensitive detection of Mycobacterium tuberculosis (M. Tb) in cerebrospinal fluid is crucial in the diagnosis of tuberculous meningitis (TBM), but conventional diagnostic technologies have limited sensitivity and specificity or are time-consuming. In this work, a novel, highly sensitive molecular diagnostic method, one-tube nested PCR-lateral flow strip test (OTNPCR-LFST), was developed for detecting M. tuberculosis. This one-tube nested PCR maintains the sensitivity of conventional two-step nested PCR and reduces both the chance of cross-contamination and the time required for analysis. The PCR product was detected by a lateral flow strip assay, which provided a basis for migration of the test to a point-of-care (POC) microfluidic format. The developed assay had an improved sensitivity compared with traditional PCR, and the limit of detection was up to 1 fg DNA isolated from M. tuberculosis. The assay was also specific for M. tuberculosis, and no cross-reactions were found in other non-target bacteria. The application of this technique to clinical samples was successfully evaluated, and OTNPCR-LFST showed 89% overall sensitivity and 100% specificity for TBM patients. This one-tube nested PCR-lateral flow strip assay is useful for detecting M. tuberculosis in TBM due to its rapidity, high sensitivity and simple manipulation.

目的 分析家族性皮质肌阵挛震颤性癫痫(FCMTE)的临床特点.方法 对8例FCMTE患者的临床资料进行回顾性分析,总结家系的临床特点、遗传特征.结果 8例FCMTE患者,连续3代发病,男女均受累,均30岁以后起病,先后出现震颤、全面强直-阵挛发作.其中,5例伴头痛,6例有肢体震颤,4例有情绪焦虑,1例有共济失调症状.8例均于30岁以后癫痫发作,呈强直-阵挛发作.4例刺激左右正中神经记录的躯体感觉诱发电位(SEPs)可见巨大电位,未见C-反射.结论 FCMTE呈常染色体显性遗传,均发生于成人,表现为四肢末端细微震颤、强直-阵挛性癫痫发作,光刺激、情绪激动或惊吓时可诱发.服抗癫痫药有效,服用β受体阻滞剂或饮酒无效,为非进展性病程.神经电生理检查提示肌阵挛或震颤来源于大脑皮质.

Objective To study the relationship between matrix metalloproteinase-9 and carotid atherosclerosis plaque’s stability. Methods The bilateral carotid atherosclerosis of 48 asymptomatic carotid atherosclerosis patients(ACA group) and 20 normal controls(NC group) were examined with color Doppler. The serum levels of MMP-9 in all the groups were measured by enzyme linked immunosorbent assay. Results Carotid atherosclerosis plaque was not found in NC group. The serum levels of MMP-9 in ACA group were significantly higher than that in NC group(all P<0.05). In ACA group, the serum levels of MMP-9 in vulnerable plaque subgroup were significantly higher than that in stabled plaque subgroup(all P<0.05) and the serum levels of MMP-9 in stable plaque subgroup were signiifcantly higher than that in no plaque subgroup(all P<0.05). Conclusion The serum levels of MMP-9 can be serum markers of carotid atherosclerosis plaque and its stability index.

Objective To investigate mutations of CSMD3 gene in a pedigree of familial cortical myoclonic tremor with epilepsy (FCMTE).Methods Peripheral blood (5 ml) was obtained from FCMTE patients (7 cases),suspected cases,and control individuals.Polymerase chain reaction (PCR) and purification of PCR products for sequencing were used to detect the existence of mutations in 73 exons of gene CSMD3.The resulting products were subjected to agarose gel electrophoresis and gel-imaging system.The PCR amplification products were sequenced.Results The sequencing results of 73 exons were compared with CSMD3gDNA sequence in human GenBank.We neither found any DNA sequence variation nor disease-related mutations.Conclusions The family does not have a mutation in the CSMD3 gene.We need to further find the disease genes and the mutations in this family.

AIMIn this study, we genotyped eight microsatellite markers on chromosome 5 and performed linkage analyses. We aimed to establish the pathogenic gene loci in this familial cortical myoclonic tremor with epilepsy (FCMTE) pedigree.MATERIALS AND METHODSReliable clinical information was obtained on the Chinese family members. Our study performed linkage analysis across these loci to identify and further characterize the pathogenic gene locus underlying FCMTE in Chinese patients.RESULTSPositive signals (>1) were only obtained for 5p15.31-p15 (Logarithm of Odds (LOD) values 2.16 and 1.34 for D5S1957 and D5S2095, respectively; θ =0.0), supporting involvement of this region in the FCTME pedigree analyzed.CONCLUSIONGenetic analysis of a Chinese family provides further evidence for linkage of FCMTE to 5p15.31-p15.

Benign adult familial myoclonic epilepsy (BAFME) has been mapped to chromosome 8q23.3–q24.1, 2p11.1–q12.1, 5p15.31–p15.1, and 3q26.32–3q28, in Japanese, Italian, Thai, and French pedigrees, respectively. Recently, we investigated a Chinese BAFME family. Clinical and electrophysiological studies revealed that nine individuals were affected with BAFME. We aimed to establish the causative gene for this pedigree. We genotyped 17 microsatellite markers covering the four previously identified chromosome regions and performed linkage analyses. The linkage analysis data showed that the LOD score was 2.80 for D5S486 at no recombination. This suggested linkage to 5p15.31–p15.1 and excluded linkage to the other three loci (LOD score <0 at no recombination). Our study suggests that the causative gene responsible for BAFME in the Chinese pedigree may be located on chromosome 5p15.31–p15.1.

<正>帕金森病(PD)是中老年人常见的神经系统变性疾病,以黑质纹状体多巴胺(DA)能神经元变性、死亡和路易小体(Lewybody)形成为主要病理改变。临床表现以静止性震颤、运动迟缓、肌强直及姿势步态异常〔1〕为主要特征。其病因和发病机制十分复杂,至今仍未彻底明确。目前,虽然有多种药物用于治

良性成人家族性肌阵挛性癫痫(benigh adult familial myoclonic epilepsy,BAFME)是一种少见的以皮质震颤、肢体远端阵挛伴或不伴癫痫发作为主要症状的常染色体显性遗传性疾病,日本、意大利等国家均有此病的相关报道,我国也曾报道过,但未曾有合并头痛、共济失调等症状的报道.现将我院收治的8例患者的家系资料报道如下.

<正>帕金森病(PD)是一种发生于中老年人的神经系统退行性疾病,主要病理改变为中脑黑质致密部多巴胺(DA)神经元变性、死亡和胞质中Lewy小体形成。其主要临床表现包括静止性震颤、肌强直、运动迟缓和姿势步态异常等,还可出现认知功能下降、情绪障碍等非运动症状。通常人们只关注PD的运动症状及体征,但是对其非运动症状,包括抑郁和痴呆研究较

帕金森病(PD)是一种中老年人常见的神经系统变性疾病,以黑质多巴胺能神经元变性缺失和路易小体形成为主要病理特征.主要临床表现为运动迟缓、肌强直、静止性震颤和姿势步态异常等[1].

<正>Moyamoya病又称脑底异常血管网病,或烟雾病,是以双侧颅内颈内动脉末端及大脑前、中动脉起始部狭窄或闭塞和颅底软脑膜、穿通动脉等小血管代偿增生为主要病理特点的慢性进展性疾病,一旦发生症状,以血管闭塞脑血流下降导致的脑梗

<正>近年来,发现离子通道异常参与帕金森病(PD)的发病,故帕金森病在某种意义上是一种"离子通道病"。KATP通道作为一种新型离子通道,得到广泛关注。随着中枢神经系统KATP通道研究的不断深入,其在帕金森病发病机制及治疗中的研究也取得了初步进展,本文就此作一综述。1 KATP通道在中枢神经系统的分布及其生物学特点KATP通道是由Kir内向整流钾通道Kir6.x与ATP结合

The mutation of the leucine-rich repeat kinase2 gene (LRRK2) is the most commonly detected genetic determinant of Parkinson's disease (PD). However, the specific role of the LRRK2 mutation in the occurrence of the autosomal-dominant family PD remains to be elucidated. In this study, we report a large Chinese LRRK2-related PD family with 33 members of four generations. Genomic DNA was isolated from peripheral blood specimens of 11 family members. The common LRRK2 mutations were screened by polymerase chain reaction, followed by polymorphic restriction enzyme digestion or direct DNA sequencing. We detected the G2385R mutation, a substitution at codon 2385 to produce a glycine-to-arginine phenotype, in two affected cases and one suspected case. Our data support the concept that the LRRK2 G2385R mutation may be involved in the pathogenesis of PD in this family.

Studies have shown that PARK1 gene is associated with the autosomal dominant inheritance of Parkinson's disease. PARK1 gene contains two mutation sites, namely Ala30Pro and Ala53Thr, which are located on exons 3 and 4, respectively. However, the genetic loci of the pathogenic genes remain unclear. In this study, blood samples were collected from 11 members of a family with high prevalence of Parkinson's disease, including four affected cases, five suspected cases, and two non-affected cases. Point mutation screening of common mutation sites on PARK1 gene exon 4 was conducted using PCR, to determine the genetic loci of the causative gene for Parkinson's disease. Gene identification and sequencing results showed that a T base deletion mutation was observed in the PARK1 gene exon 4 of all 11 collected samples. It was confirmed that the PARK1 gene exon 4 gene mutation is an important pathogenic mutation for Parkinson's disease.

Notch signaling plays a complex role in human malignancies. It can affect cell proliferation, differentiation and apoptosis either positively or negatively, depending on cell type. In the present study we measured the expression of Notch1 in clinical glioma specimens and investigated a possible association between Notch1 expression and World Health Organization grade. Ninety-eight gliomas plus adjacent normal tissue and 26 specimens of normal control tissue were collected, and expression of Notch1 mRNA and protein were assessed using quantitative real-time polymerase chain reaction, western blot and immunohistochemical analysis. We found that Notch1 mRNA and protein were expressed at higher levels in gliomas than in the adjacent tissue or in control brain tissue (p<0.05). Moreover, expression of Notch1 was closely associated with glioma progression, since expression levels increased from grade I to grade IV disease (p<0.05). Notch1 expression was also significantly associated with Karnofsky performance scale (KPS) score: Notch1 expression was significantly higher in patients with a lower KPS score (p<0.05). These findings confirm that Notch1 expression is upregulated in glioma and suggest it is related to tumor progression. If Notch1 plays an important oncogenic role in glioma progression, it may be a potential diagnostic and therapeutic target.

目的 探讨左旋多巴对帕金森病(PD)大鼠黑质多巴胺(DA)能神经元毒性的影响.方法 采用6-OHDA制备轻度损伤和重度损伤的PD大鼠模型,口服大剂量(100 mg/kg)和小剂量(25 mg/kg)美多巴1～3个月,通过酪氨酸羟化酶(TH)免疫组化染色,观察左旋多巴对PD大鼠残存的黑质DA能神经元的影响.结果 轻、重度损伤组中,大剂量喂药组、小剂量喂药组和不喂药组三组之间DA能神经元差异无显著性(P>0.05).结论 长期使用左旋多巴对6-OHDA毁损的PD大鼠残存的黑质DA能神经元无毒性作用.

Marcus Gunn现象,又称张口睁眼现象、张口提上睑连带运动综合征(jaw-win-king levator palpebrae synkinesis syndrome),为一种少见的先天性疾病,有家族遗传倾向,为不规则常染色体显性遗传,约占先天性上睑下垂的5%.Rober Marcus Gunn于1883年首次报道的,并以其名字命名.我国于1959年罗文彬等[1]最先报道.有学者认为该病与三叉神经参与提上睑肌的支配有关,由于三叉神经核的翼外神经部分与提上睑肌的神经核区域之间存在某种联系,或由于三叉神经与动眼神经之间在周围发生运动性联系所致[2].获得性者可发生于任何年龄,多与脑外伤、肿瘤或手术后有关.