宁夏地区回、汉族脊髓小脑共济失调家系SCA3/MJD基因突变研究

目的通过对宁夏地区临床诊断为脊髓小脑共济失调的3个家系(2个汉族家系、1个回族家系)进行SCA3/MJD基因检测,探讨脊髓小脑共济失调的发病机制与临床特点,以为临床应用提供依据。方法对3家系受试者进行神经系统检查和系谱调查,部分行头部MRI和肌电图检查,以及SCA3/MJD基因胞嘧啶-腺嘌呤-鸟嘌呤(CAG)重复数目检测。结果3家系中共计8例脊髓小脑共济失调患者(汉族家系1中6例、汉族家系2中1例和回族家系中1例),符合常染色体显性遗传特点,以共济失调与构音障碍为主要表现,其次为眼外肌麻痹、眼球震颤、慢眼动、锥体束征等。其中汉族家系1和回族家系明确诊断为SCA3/MJD家系,两家系中7例患者(汉族家系1中6例、回族家系中1例)及2例临床表型正常亲属(两家系中各1例)检测出SCA3/MJD异常等位基因,其CAG重复数目为66～81次。汉族家系2中1例患者及汉族家系1中4例临床表型正常亲属SCA3/MJD基因CAG重复数目为20～33次。正常等位基因与异常等位基因CAG重复数目差异有统计学意义(t=5.309,P=0.000)。结论宁夏地区回、汉族脊髓小脑共济失调患者中存在SCA3/MJD基因型,基因检测分析有利于明确诊断脊髓小脑共济失调且能够检出症状前患者。     

马查多-约瑟夫病/脊髓小脑型共济失调Ⅲ型患者(CAG)n拷贝数与临床特征

目的探讨马查多约瑟夫病基因１（ＭＪＤ１）ＣＡＧ三核苷酸动态突变及其拷贝数与ＭＪＤ／脊髓小脑型共济失调Ⅲ型（ＳＣＡ３）患者临床特征的相关关系。方法应用聚合酶链式反应、变性聚丙烯酰胺凝胶电泳和银染技术，对９个ＭＪＤ／ＳＣＡ３家系１０９名成员进行ＭＪＤ１基因（ＣＡＧ）ｎ拷贝数分析。结果发现异常扩增的（ＣＡＧ）ｎ拷贝数与发病年龄呈负相关，并在一定程度上影响病情严重程度；主要临床症状、体征与异常扩增的（ＣＡＧ）ｎ拷贝数无关，而是受病程影响。同时发现１７例症状前患者。结论异常扩增的（ＣＡＧ）ｎ拷贝数对疾病表型有影响，但不能完全作为临床特征的预测指标     

脊髓小脑性共济失调1家系5代6例报告

1 病例报告 先证者(Ⅲ2),男,51岁,工人.因"步态不稳10年",于2012-07-25以"脑梗死后遗症"收住作者医院.患者10年前无明显原因出现步态不稳,4年前出现左下肢无力,易跌倒.2006年开始就医,曾在外院多次以"脑梗死"治疗无效,且逐渐加重.患者无意识及大小便障碍.既往有高血压病史8年,未规律治疗.2008年因跌倒致左胫骨下段骨折,行切开复位内固定治疗,已愈.入院检查:体温36.2℃,心率74次/min,呼吸18次/min,血压150/94mmHg.意识清楚,语言欠清晰,心肺检查未见异常.     

脊髓小脑性共济失调3型一家系报道

正1病例报告患者(先证者,Ⅳ4)男,58岁,因"渐进性步态不稳、言语含糊6年,卧床3年,抽搐2h"于2015-03-16入作者医院。患者2009年开始无明显原因出现步态不稳,言语含糊,取物不准,病程呈进行性加重。2012年开始患者行走不能,言语不清症状加重。患者自2012年开始卧床。本次入院前2h无明显诱因出现发作性肢体抽搐伴短     

酪蛋白激酶2结合并磷酸化ataxin-3

目的 马查多-约瑟夫病/脊髓小脑共济失调3型,是由MJDI基因产物ataxin-3的C-末端的多聚谷氨酰胺发生重复扩展突变而引起的一种常染色体显性遗传的神经退行性疾病,目前它的发病机制还不清楚.很多研究表明磷酸化修饰作用在很多神经退行性疾病的发病过程中起到重要作用,然而已知可以磷酸化ataxin-3的激酶仍然很少.本研究的目的是探讨酪蛋白激酶2(Casein kinase 2,CK2)对于ataxin-3的磷酸化作用.方法 通过GST pulldown和免疫共沉淀技术鉴定ataxin-3和CK2的相互作用.通过体外磷酸化技术检测CK2对ataxin-3的磷酸化.结果 (1)正常和扩展突变型ataxin-3在体外与CK2α、β亚单位均发生相互作用;(2)在293细胞中正常和扩展突变型ataxin-3只和CK2β亚单位相互作用,而与α亚单位没有结合;(3)正常和扩展突变型ataxin-3都可以被CK2磷酸化.结论 Ataxin-3是蛋白激酶CK2的底物.     

脊髓小脑性共济失调3型一家系的临床表现分析

目的 探讨1个脊髓小脑性共济失调3型(SCA3)家系中患者的临床表现,分析影响其特征、异质性及严重程度的原因。方法 采用PCR、琼脂糖凝胶电泳的方法对1个脊髓小脑性共济失调家系进行基因检测明确分型并获得等位基因内CAG三核苷酸重复扩增次数; 对比该家系中5例患者的典型症状、非典型症状,了解其临床异质性并分析产生原因。结果 确定该家系为脊髓小脑性共济失调SCA3型,发现3名表现正常的女性携带者。CAG重复次数与病程长短呈负相关(r=-0.942,P<0.05); 病程与共济失调严重程度呈正相关(r=1.000,0.913,P<0.01)。结论 该家系所有患者以明显共济失调及构音障碍为临床特征,特别是躯干及下肢的共济失调; CAG重复次数、病程及共济失调严重程度之间有明显相关性; 认知功能障碍随着疾病的进展逐渐显现; 眼肌麻痹、括约肌功能障碍或吞咽困难与CAG重复次数之间无明显关系但增加疾病持续时间; 锥体束受损及严重程度可能提示预后不良。     

脊髓小脑性共济失调3型的临床与分子生物学特征

目的探讨脊髓小脑性共济失调(SCA)3型的临床与分子生物学特征。方法对2个SCA家系中12例患者的临床表现、头颅影像学资料进行分析,并与15名家系中未发病成员(家系对照组)及12名非血缘关系的健康对照者(健康对照组)的SCA3、SCA1及SCA7基因目的片段CAG重复数目进行比较。结果2个家系4代27名成员中共有12例发病,每代均有患者,男女均受累,起病年龄平均32岁,以行走不稳、动作笨拙和言语含糊为突出表现;头颅MRI示小脑、脑干明显萎缩;各组SCA1及SCA7基因CAG检测均在正常范围;SCA3目的片段CAG两对照组重复11～39次,10例患者为65～87次,确诊为SCA3;家系1的Ⅳ2现年8岁,临床无异常表现,CAG重复数目分别为21次和64次,可能是未到发病年龄的症状前患者。结论SCA3为常染色体显性遗传性疾病,临床均以共济失调和构音障碍为突出表现,CAG重复数目检测可为基因诊断和症状前诊断提供依据。     

宁夏地区脊髓小脑性共济失调家系基因突变特征的研究

目的研究宁夏地区脊髓小脑性共济失调(SCA)患者基因突变的特征。方法用聚合酶链反应(PCR)、毛细管凝胶电泳(CGE)及DNA测序方法对1个临床诊断为SCAs的宁夏籍家系中6例SCA患者和4名亲属进行SCA3/Machado-Joseph disease(MJD)基因三核苷酸CAG重复序列检测。结果此家系中6例患者及1名表型正常的家系成员检测出异常SCA3/MJD等位基因,CAG重复数为66～81次;确诊为SCA3/MJD。其余3名家系成员CAG重复数正常(22～33次)。结论宁夏地区SCAs患者有SCA3/MJD亚型。提示基因检测对SCAs患者的明确诊断及分型有重要意义。     

脊髓小脑性共济失调一家系的基因诊断

目的 对1个常染色体显性遗传的脊髓小脑性共济失调(SCA)家系进行基因诊断.方法 采用PCR技术,对一汉族SCA家系(包括3例患者及3位无症状成员)及50名正常对照者的SCA1 ～3基因进行检测,通过琼脂糖凝胶电泳和产物直接测序法计数等位基因内CAG三核苷酸重复次数.结果 该家系中所有成员SCA1、SCA2基因CAG三核苷酸重复次数在正常范围;3例患者SCA3 CAG重复次数分别为67、68和66次,1位无症状成员为71次.结论 该家系为SCA3,基因检测诊断出1例症状前患者.     

小脑性共济失调13例病例报道

目的:探讨以进行性小脑性共济失调为主要临床症状的疾病诊断。方法:回顾性分析13例以慢性进行性小脑共济失调为主要临床表现患者的临床资料、实验室、影像学和基因检查结果。结果:13例患者中,脊髓小脑性共济失调3例,多系统萎缩-小脑型6例,小脑肿瘤1例,桥小脑结合臂脓肿1例,小脑梗死后遗症2例。结论:对于以进行性小脑共济失调为主要体征的患者,临床上首先要排除占位性病变,其次多系统萎缩和脊髓小脑性共济失调为主要的遗传变性病因。     

Autosomal dominant cerebellar ataxia type I in Morocco: presence of the SCA1 and SCA3/MJD mutations

We searched for CAG repeat expansions at the SCA1 and SCA3/MJD loci in nine families, including 15 examined patients, with autosomal dominant cerebellar ataxia type I from Morocco. Expansion of the CAG repeat was found in one family at the SCA1 and two at the SCA3/MJD locus, demonstrating the existence of genetic heterogeneity among ADCA type I families in Morocco. Instability during transmission was observed at both loci as in other unstable mutations. The phenotypes of the SCA1 and SCA3/MJD patients were similar.     

A case of Machado-Joseph disease presenting pure cerebellar ataxia]

We report a 61-year-old woman with Machado-Joseph disease (MJD) presenting with pure cerebellar ataxia. The patient exhibited an unsteady gait at the age of 51 years. She was admitted to our hospital at the age of 61 years. Her older brother had been diagnosed as having spinocerebellar degeneration (SCD). Our patient showed gaze-evoked nystagmus, wide-based gait, slight lack of coordination of the four extremities, mildly ataxic speech and slight decrease in the bilateral Achilles tendon reflexes. Babinski's sign was absent. Sensory impairments were not present and muscle tone and muscle strength were normal. There was no autonomic dysfunctions. MRI revealed moderate atrophy of the cerebellum and pons. We performed gene analysis of SCD using white blood cells from the patient, and the analysis showed 70 CAG repeats in the MJD1 gene, which is an abnormally high number of repeats. Compared with three reported cases of MJD presenting pure cerebellar ataxia, only our patient showed a nasal voice. The number of CAG repeats in the MJD1 gene of our patients was the most prolonged of the four cases. MJD should be considered in patients with familial SCD even if their neurological signs and symptoms outside the cerebellum are not obvious.     

Phosphodiesterase 10A autoimmunity presenting as cerebellar ataxia responsive to plasma exchange: a case report

Journal of Neurology -     

Internuclear ophthalmoplegia and cerebellar ataxia: report of one case.

Deep hemispheric or brainstem small infarcts can lead to atypical lacunar syndromes. Unilateral internuclear ophthalmoplegia (INO) and cerebellar ataxia has not been reported previously. A 57-year-old hypertensive female presented with bilateral appendicular and left truncal cerebellar ataxia and right INO. Cranial MRI showed a right paramedian infarct of lacunar size located in the tegmentum of caudal mesencephalon. At this level the involvement of medial longitudinal fascicle (MLF) led to right INO and the lesion of brachium conjunctivum caused the bilateral cerebellar ataxia. Ipsilateral involvement of both cerebellofugal fibers, before and after decussation, was responsible for bilateral cerebellar ataxia.     

Wolfram's syndrome presenting as a cerebellar ataxia

INTRODUCTION: Wolfram syndrome is a genetic disease with recessive autosomic transmission, associating early-onset diabetes mellitus and bilateral optical atrophy. CASE REPORT: We report the case of a 47-year-old patient for whom we diagnosed a Wolfram syndrome in view of a late neurological syndrome in association with ataxia and bilateral horizontal nystagmus. The brain resonance magnetic imaging revealed a major atrophy of the brainstem and cerebellum. CONCLUSION: Wolfram syndrome is a rare pathology, with fatal consequences before the age of 50. The association of diabetes mellitus and optical atrophy, especially when there are other symptoms (ataxia, deafness, diabetes insipidus, neuropsychiatric manifestations or urinary tract disorders) should lead to this diagnosis and to carry out a genetic confirmation.     

康复综合疗法治疗小脑共济失调一例

正患者女性,29岁。主因言语不清、双侧肢体活动失衡3月余,于2014年10月10日入天津市环湖医院就诊。患者入院前4个月顺产一女婴,产褥期第10天出现发热,体温37.3~38.6℃,伴乏力,经当地医院退热处理后体温降至37.3~37.6℃,乏力症状稍有缓解;产褥期第14天体温突然升至41℃,伴寒战和意识不清,遂入外院急救中心重症监护病房(ICU)抢救。考虑为中暑,并可疑颅内感染、缺氧缺血性脑病(HIE)、代谢性脑病;脓毒血症;肺炎;双     

Age related axonal neuropathy in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD)

To identify determinants of peripheral involvement in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) the influence of CAG repeat length, age of onset, disease duration and age on the results of nerve conduction studies was analysed in 58 patients with SCA3/MJD. Patients with SCA3/MJD showed marked reduction of compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes indicating axonal neuropathy of both motor and sensory fibres. In addition, there was moderate slowing of nerve conduction suggestive of mild peripheral demyelination. Multivariate regression showed that CMAP and SNAP amplitudes decreased with age, but were not affected by CAG repeat length, age of onset, or disease duration. The age related decline of CMAP and SNAP amplitudes in SCA3/MJD was greater than in normal subjects. The data suggest that the degree of peripheral damage in SCA3/MJD does not depend on CAG repeat length, age of onset, or disease duration, but is mainly related to the time period over which the SCA3/MJD mutation exerts its effect.     

Dystonia as presenting manifestation of ataxia telangiectasia : a case report

Ataxia telangiectasia is a genetically inherited multisystem disorder with predominant feature being telangiectasia and cerebellar ataxia. In this report, a family of three siblings suffering from ataxia telangiectasia is described. The proband presented with dystonia and dystonic myoclonus, both of which are rare presenting features of ataxia telangiectasia.     

Regional differences in genetic subgroup frequency in hereditary cerebellar ataxia, and a morphometrical study of brain MR images in SCA1, MJD and SCA6.

Molecular genetic assessments of 69 individuals in 44 families with hereditary cerebellar ataxia (HCA) were made to determine the relative frequencies of subtypes of HCA in Yamagata, Japan. Fifteen families (34%) had SCA1, none had SCA2, nine (20%) had MJD, five (11%) had SCA6 and nine (20%) had DRPLA. These findings differ markedly from those in other regions of Japan and the rest of the world. A morphometrical study of the brain MR images also was made on 38 individuals with SCA1 (n = 14), MJD (n = 8) or SCA6 (n = 16). In SCA1, the ventral pons was atrophic in proportion to the amount of cerebellar atrophy. In MJD, both the pons and the cerebellum were atrophic, cerebellar atrophy being less pronounced than that in SCA1 and SCA6. While both the major and minor axes of the ventral pons were proportionally decreased in SCA1, the minor axis was more decreased than the major axis in MJD. In SCA6, a mild reduction in the ratio of the ventral pontine area to the posterior fossa area (Pv/PF) was observed as well as obvious cerebellar atrophy. These findings indicate that in MR images SCA1, MJD and SCA6 show different atrophic features of the cerebellum and brainstem.