两个亨廷顿舞蹈病家系IT15基因的研究

为了探讨亨廷顿舞蹈病家系患者的临床特征与IT15基因中(CAG)_n重复拷贝数之间的相互关系, 对两家系患者的临床、影像学特征、发病年龄及遗传方式等进行分析; 用聚合酶链反应技术、6%聚丙烯酰胺凝胶电泳及直接测序等方法, 对42名家系成员的IT15基因的(CAG)_n三核苷酸重复序列进行分析。结果显示家系1患者无典型的临床“三联症”及尾状核的萎缩, 18名家系成员中9名患者IT15基因的(CAG)_n拷贝数介于40~50次之间,拷贝数与发病年龄无明显相关; 而家系2患者具有典型的“三联症”和尾状核的萎缩, 24名家系成员中5例患者(CAG)_n拷贝数大于等于50次, 发病年龄与(CAG)_n拷贝数相关。因此亨廷顿舞蹈病患者的临床特征在一定程度上受IT15基因的(CAG)_n三核苷酸重复拷贝数的影响, 拷贝数大于50次, 发病年龄与(CAG)_n拷贝数相关, 并有经父系遗传的(CAG)_n拷贝数的扩展, 且存在遗传早现现象。     

MJD基因CAG不稳定性扩增与临床研究

为了解Ｍａｃｈａｄｏ－ Ｊｏｓｅｐｈ 病（ＭＪＤ）基因突变及临床的神经电生理特点, 对１６ 个诊断为遗传性小脑性共济失调（ＳＣＡ）家系的４５ 例病人及３０ 例家系的“正常”人作ＭＪＤ 基因突变分析,检出ＭＪＤ 基因的病人行肢体运动及感觉神经传导速度（ＭＣＶ 及ＳＣＶ）、脑干诱发电位（ＢＡＥＰ）,视觉诱发电位（ＶＥＰ）的检查。结果检出１０ 个家系２５ 例病人及１ 例症状前１８ 岁女孩有ＭＪＤ基因突变,ＣＡＧ 三核苷酸重复７３～７９ 次,异常等位基因片段长３８０～４０２ｂｐ,均为杂合子; 正常人ＣＡＧ 三核苷酸重复１８～４０ 次,等位片段长２００～２７０ｂｐ,电生理发现ＭＪＤ 的ＳＣＶ 减慢比ＭＣＶ 明显,而下肢的ＭＣＶ、ＳＣＶ 又较上肢明显,ＢＡＥＰ、ＶＥＰ均有不同程度的潜伏期延长或波的异常;ＭＪＤ 的父亲遗传早于母亲,进展也较块,临床以小脑性共济失调为突出症状,其次为构音障碍、突眼等,肌肉萎缩仅见于晚期病人;ＭＲＩ示小脑萎缩较明显,脑干萎缩并不严重,未见明显的颈髓萎缩。     

MJD基因CAG不稳定性扩增与临床研究

为了解Machado-Joseph病(MJD)基因突变及临床的神经电生理特点, 对16个诊断为遗传性小脑性共济失调(SCA)家系的45例病人及30例家系的“正常”人作MJD基因突变分析,检出MJD基因的病人行肢体运动及感觉神经传导速度(MCV及SCV)、脑干诱发电位(BAEP),视觉诱发电位(VEP)的检查。结果检出10个家系25例病人及1例症状前18岁女孩有MJD基因突变,CAG三核苷酸重复73～79次,异常等位基因片段长380～402bp,均为杂合子; 正常人CAG三核苷酸重复18～40次,等位片段长200～270bp,电生理发现MJD的SCV减慢比MCV明显,而下肢的MCV、SCV又较上肢明显,BAEP、VEP均有不同程度的潜伏期延长或波的异常;MJD的父亲遗传早于母亲,进展也较块,临床以小脑性共济失调为突出症状,其次为构音障碍、突眼等,肌肉萎缩仅见于晚期病人;MRI示小脑萎缩较明显,脑干萎缩并不严重,未见明显的颈髓萎缩。 Abstract:　To investigate the gene mutation of clinical and neuroelectrophysiological characteristics in Machado-Joseph disease(MJD). The gene mutation was detected in 45 patients diagnosed as spinocerebellar ataxia(SCA) and 30 “healthy relatives”. Brain stem evoked potentials(BAEP), visual evoked potentials(VEP) and motor conduction velocity (MCV) and sensory conduction velocity (SCV) were performed on MJD. Gene mutations were detected in 25 patients and a 18-year-old girl among 16 families. Trinucleotide repeats of CAG were 73～79. The fragments of abnormal alleles were 380～402bp, and all patients were heterozygous. The copy numbers of normal alleles were 18～40, fragments from 202～270bp. SCV reduction was much obvious compared to MCV, MCV and SCV in lower limb ?ere much more slow than that in upper's. BAEP, VEP were also delayed in latency. The anticipation in parental sex bias were much more obvioius than that in matental's. Cerebellar ataxia was most severe, the next were dysarthria and bulging eyes. Amytrophy was seen only in bed ridden patients. Cerebellar atrophy was more severe than brain stem, cord atrophy was n't observed in all MJD.