脊髓小脑性共济失调12型的分子遗传学诊断及临床分析

[目的]研究分析脊髓小脑性共济失调12型(SCA12)的分子诊断及临床表现特征。[方法]对临床诊断为脊髓小脑性共济失调(SCA)的36个家系43例患者、38例散发患者、60名家系“健康”个体及44名正常对照，通过聚合酶链反应(PCR)对SCA12基因含有CAG三核苷酸重复片段进行扩增，并利用ABI373测序仪对异常等位基因片段进行DNA测序，聚丙烯酰胺凝胶电泳并以图像分析软件计算其长度，推算所有正常和异常扩增等位基因内CAG重复次数。[结果]正常我国南方汉族人群SCA12等位基因CAG重复数目为22～27。检出1个家系患者1例，症状前患者2例，两个等位基因中一个异常等位基因内CAG重复数目为68次。[结论]SCA12比较罕见，CAG三核苷酸重复异常扩增是其致病原因，分子遗传学分析可确证临床诊断和症状前诊断，并可为遗传咨询提供依据。该例为国内首次报道。     

脊髓小脑性共济失调7型的分子遗传学诊断及临床分析

目的 研究分析脊髓小脑性共济失调7型(SCA7)的分子遗传学诊断、应用以及临床表现特征。方法 对临床诊断为SCA的36个家系43例病人、38例散发SCA患者、60名家系“健康个体”以及44名非家系正常对照人员,通过PCR及聚丙烯酰胺凝胶电泳等技术检测SCA7基因位点内CAG三核苷酸重复扩增次数,并利用ABI373测序仪对异常等位基因片段进行DNA测序。结果 我国南方正常人群SCA7等位基因CAG重复数为9~19。检出2个家族性、1个散发性共3例SCA7患者,测序证实其异常等位基因内CAG重复数目分别为65、65、63。结论 SCA7基因内部CAG三核苷酸重复异常扩增是该病致病原因,利用分子遗传学分析可进行基因诊断,为症状前诊断及遗传咨询提供依据。     

脊髓小脑性共济失调7型的分子遗传学诊断及临床分析

目的 研究分析脊髓小脑性共济失调7型(SCA7)的分子遗传学诊断、应用以及临床表现特征。方法 对临床诊断为SCA的36个家系43例病人、38例散发SCA患者、60名家系“健康个体”以及44名非家系正常对照人员，通过PCR及聚丙烯酰胺凝胶电泳等技术检测SCA7基因位点内CAG三核苷酸重复扩增次数，并利用AB1373测序仪对异常等位基因片段进行DNA测序。结果 我国南方正常人群SCA7等位基因CAG重复数为9～19。检出2个家族性、1个散发性共3例SCA7患者，测序证实其异常等位基因内CAG重复数目分别为65、65、63。结论 SCA7基因内部CAG三核苷酸重复异常扩增是该病致病原因，利用分子遗传学分析可进行基因诊断，为症状前诊断及遗传咨询提供依据。     

云南地区汉族脊髓小脑共济失调3型SCA3/MJD患者的临床特点及遗传学研究

目的通过对云南地区临床诊断为脊髓小脑共济失调的家系进行SCA3基因检测,探讨汉族人群遗传性脊髓小脑共济失调3型(spinocerebellar ataxia type 3,SCA3)患者临床特点与遗传学特征。方法对4个家系26例脊髓小脑共济失调患者进行神经系统检查和家系谱调查,应用聚合酶链反应(PCR)、琼脂糖凝胶电泳和基因测序等技术进行SCA3基因内CAG三核苷酸重复序列,并对异常等位基因片段进行DNA测序。结果临床表现以共济失调和构音障碍为主,其次表现为锥体束征、眼部症状等,认知功能障碍较少见。检出4个家系(26例患者)为SCA3,符合常染色体显性遗传特点,测序证实其异常等位基因CAG重复数目在67～82次之间。结论云南地区汉族的SCAs患者以SCA3型为主,主要表现为共济失调和构音障碍,基因检测仍是其诊断的金标准。     

遗传性脊髓小脑型共济失调病人SCA3基因突变检测

①目的 探讨遗传性脊髓小脑型共济失调（SCA）病人SCA3基因突变的意义。②方法 应用聚合酶链反应（PCR）、聚丙烯酰胺凝胶电泳银染法,对临床诊断为SCA的15个家系的32例病人及其有亲缘关系的22例正常者,进行SCA3基因内一段包含CAG三核苷酸重复序列片段扩增。③结果 5个家系中的21例病人各有1个SCA3异常等位基因扩增片段,其中1个家系中2例病人和1例“正常者”的1个等位基因的CAG三核苷酸重复数目都为48次。④结论 检测SCA基因的动态突变是目前诊断SCA的唯一有效方法。     

遗传性脊髓小脑型共济失调病人SCA_3基因突变检测

1目的　探讨遗传性脊髓小脑型共济失调 (SCA)病人 SCA3基因突变的意义。2方法　应用聚合酶链反应 (PCR)、聚丙烯酰胺凝胶电泳银染法 ,对临床诊断为 SCA的 15个家系的 32例病人及其有亲缘关系的 2 2例正常者 ,进行 SCA3基因内一段包含 CAG三核苷酸重复序列片段扩增。3结果　 5个家系中的 2 1例病人各有 1个 SCA3异常等位基因扩增片段 ,其中 1个家系中 2例病人和 1例“正常者”的 1个等位基因的 CAG三核苷酸重复数目都为 48次。4结论　检测 SCA基因的动态突变是目前诊断 SCA的唯一有效方法。     

遗传性脊髓小脑型共济失调7型三家系临床特征及分子生物学研究

目的研究中国人遗传性脊髓小脑型共济失调7型（SCA7）的临床和分子生物学特征。方法应用聚合酶链反应、聚丙烯酰胺凝胶电泳、毛细管电泳等技术,检测临床诊断为脊髓小脑型共济失调（SCA）的184个家系245例患者和71例散发SCA患者以及163名正常人的SCA7基因内CAG三核苷酸重复次数,对异常等位基因片段进行DNA测序,并对其中一个大家系进行连锁分析。结果检出3个SCA7家系（15例患者）,阳性率为1．6％,测序证实异常等位基因的CAG重复次数为38-71次,其他SCA患者以及正常人的SCA7等位基因CAG重复次数为6-15次。其中2个家系存在遗传早现现象,特别在父系遗传时更明显。对其中一个家系进行连锁分析结果在微卫星标记D3S1300处获得两点最大LOD值为2．82（θ=0．00）。结论SCA7是少见的SCA亚型。SCA7基因异常重复突变是SCA7的致病原因,38次CAG重复是目前国内报道的SCA7最小的病理性扩增。     

脊髓小脑性共济失调一家系的遗传学研究

目的对一个常染色体显性遗传的脊髓小脑共济失调家系(spinocerebellar ataxias,SCA)进行基因诊断并探讨其临床特点。方法完成家系调查和系谱分析,通过聚合酶链式反应和直接测序的方法对收集到的家系成员进行脊髓小脑性共济失调致病基因CAG三核苷酸重复数目的检测。结果该家系呈常染色体显性遗传模式,家系中3名患者均于30岁后逐渐表现为行走不稳、饮水呛咳、言语不清等共济失调的临床特征。对所有家系成员进行基因诊断,结果发现,SCA2和SCA3致病基因的CAG重复数目均在正常范围内;而家系中3名患者SCA1致病基因出现异常等位基因,CAG扩增次数分别为43、48和51次,另有2名成员GAG重复次数分别为53次和50次,诊断为症状前患者。结论该家系为三核苷酸重复序列(CAG)动态突变引起的常染色体显性遗传脊髓小脑共济失调Ⅰ型,基因诊断还发现家系中2名症状前患者。     

河南汉族一脊髓小脑性共济失调家系基因突变检测

目的检测和分析河南汉族一脊髓小脑性共济失调(SCA)家系亚型分型。方法采用聚合酶链式反应(PCR)技术和DNA直接测序法分析该家系患病者SCA1、SCA2、SCA3、SCA6、SCA7、SCA12、SCA17共7种常见SCA亚型基因序列,并与家系中其他正常个体及50例健康个体基因序列进行比较分析。结果检测到该家系4例患者及家系中2例健康成员SCA3基因的1个等位基因三核苷酸序列CAG异常重复扩增,异常重复次数在71~81次。其余6种亚型基因检测无异常。结论该家系SCA患病表现为中国人常见的SCA3亚型,家系中2例健康成员可能为症状前患者。     

脊髓小脑共济失调症1例

目的探讨脊髓小脑共济失渊症（spinocerebellar ataxia,SCA）基因诊断的方法。方法根据患者的临床表现及我国该病发病率．通过聚合酶链反应,对一例患者的SCAI、SCA2、SCA3三个基因的三核骨酸重复片段进行扩增,然后通过琼脂糖凝胶电泳和PCR产物直接测序的方法确定异常扩增等位基【大I内的CAG三核苷酸重复数目。结果该患者SCA3致病基因出现异常等位基因,CAG扩增次数为67次。结论临床表现为脊髓小脑共济失调症患者,结果可通过实验室的基闪诊断进行确诊。     

Trinucleotide repeat expansion of spinocerebellar ataxia (SCA1) found in a Chinese family.

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Clinical and genetic study of spinocerebellar ataxia type 7 in East Asian population

Background Spinocerebellar ataxia type 7 （SCA7） is known as an autosomal dominant cerebellar ataxia; patients with genetically confirmed diagnoses of SCA7 have increased rapidly in recent years.However, SCA7 is a rare subtype of SCA, and most data available about SCA7 are those of white people.The aim of the present study was to systematically review the prevalence and clinical and genetic aspects of SCA7 patients in East Asian population.Methods A search for publications on SCA7 was performed by using the ＂PubMed＂ database with the published language limited in English.Publications mainly focusing on the prevalence of SCA7 in patients with SCA and the clinical and genetic features of SCA7 patients were fully reviewed and analyzed.Results The prevalence of SCA7 in SCA patients ranged from 0 to 7.7%, which was similar to those reported previously.The clinical manifestations were typically present at the 30＇s of its victims （median, 29 years; interquartile range （IQR）,19.5-36.5 years）, and the symptoms appeared 15 years （（15.17±4.22） years） earlier on average in the offspring than in the parents.Gait ataxia and visual impairment were both found in all patients of whom the clinical features were described.Mutant SCA7 alleles contained 40-100 CAG repeats, with a median of 47 repeats （IQR, 44.5-50.0）; and the offspring had 13 more repeats on average compared with their parents （12.62±19.03）.A strong negative correlation was found between CAG repeat size and the onset age of patients （r=-0.739, P=0.000）.In addition, no significant difference was found in CAG repeat sizes between patients with visual impairment as the initial symptom and those with gait disturbance as their initial symptom （P=0.476）.Conclusions The prevalence of SCA7 in SCA patients, the age at onset and CAG repeats of SCA7 patients in East Asia are consistent with those of white people.However, larger population study is needed to assess the correlation between the CAG repeat size and initial symptoms of SCA7 patients in East Asia.     

Clinical Characteristics,Radiological Features and Gene Mutation in 10 Chinese Families with Spinocerebellar Ataxias

Background:

Spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs.

Methods:

In this study, we investigated 10 SCAs Chinese families with SCA1, SCA3/Machado–Joseph disease (MJD), SCA7, SCA8. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but failed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were performed.

Results:

We found that SCA3/MJD was the most common subtype in Han population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively correlated with the number of cytosine-adenine-guanine (CAG) repeats; the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset.

Conclusions:

Collectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.     

中国人群遗传性共济失调症中脊髓小脑共济失调1亚型的基因分型与诊断

研究中国人群遗传性共济失调症中脊髓小脑共济失调1亚型（SCA1）的基因分型与诊断。在D65274与D6S89之间设计一对引物扩增CAG三核苷酸重复序列。结果：在收集的来自8个家系的9例遗传性共济失调患者中发现1个家系中的2例患者在此SCA1基因位点表现为杂合子，其中的一个等位基因均存在扩展现象，表现为SCA1亚型；而其他患者及健康人表现为纯合子。结论：中国人群SCA1亚型在常染色体显性遗传性共济失调症中所占比例为14％，SCA1亚型的遗传结构与白种人相似。