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。     

幽门螺杆菌细胞毒素相关蛋白A对人胃腺癌上皮AGS细胞蛋白质组的影响

为明确幽门螺杆菌细胞毒素相关蛋白A(CagA)在致病过程中对宿主细胞蛋白质表达的影响及其与CagA磷酸化的相关性,分别用野生型cagA质粒和磷酸化位点突变型cagA质粒转染人胃腺癌上皮AGS细胞,应用表面加强激光解析电离-飞行时间质谱技术,分析细胞蛋白质组的改变。结果表明,在可捕获的400多个蛋白质中,野生型CagA可使AGS细胞质荷比为4229、4714、4728、5129、6546、6657、8162、9084、13803、14021的10个蛋白质表达上调,质荷比为2013、4286、8563、9952、11085、11645的6个蛋白质表达下调。突变型CagA只能使质荷比为4714、4728、6546和6657的蛋白质表达上调。这些结果提示,这16个差异表达蛋白质可能参与了CagA的致病过程,其中质荷比为4714、4728、6546和6657蛋白质表达的改变与CagA的磷酸化作用无关,而其余12个蛋白质表达的改变则都依赖于CagAEPIYA重复序列酪氨酸位点的磷酸化。这些发现为进一步探讨CagA的致病机制提供了实验依据。     

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.