【摘要】 目的　研究Machado Joseph病 (MJD)的基因突变及临床特征。方法　应用PCR方法结合DNA测序技术 ,检测了临床诊断脊髓小脑性共济失调 (SCA)的 11个家系 2 7例病人 ,4例散发SCA及 35名家系中“正常人”的基因突变 ,并利用ABI 373测序仪对 1例MJD与 1例症状前MJD两对等位基因片段分别进行DNA测序。结果　检出 9个家系为MJD ,其中 2个MJD家系检测到 6例症状前MJD。正常等位基因三核苷酸 (CAG)重复 14～ 36次 ,异常的则为 70～ 75次。测序表明MJD或症状前MJD的正常等位基因片段第 16、17及第 9、11、12位的CAG三核苷酸分别被CAA/GAA取代 ,CAG重复分别为 18及 14次 ;而异常的等位基因片段全部为CAG重复。结论　CAG过度扩增为MJD的致病原因 ,利用基因突变分析可提供症状前预报及遗传咨询 ,并提供诊断及鉴别诊断 ,为基因分型提供科学依据。更多还原

【Abstract】 Objective To study the characteristics of gene mutation in Chinese MJD. Methods The gene mutations of 27 patients and 35 “ healthy persons” from 11 SCA families, including 4 sporadic SCA, were detected by combining polymerase chain reaction(PCR) with DNA sequencing. The fragments of two pair alleles in one MJD and one asymptomatic MJD were sequenced by ABI 373, respectively. Results The gene mutations of 9 SCA families were MJD among which 6 asymptomatic MJD had been detected in 2 SCA families. Normal alleles of MJD have CAG repeats ranging from 14 to 36 , abnormal from 70 to 75. The positions of CAG at 16, 17 and 9, 11, 12 in fragments of normal alleles MJD were replaced by CAA/GAA, respectively. CAG repeats were 18 in MJD, 14 in asymptomatic MJD; contrarily. The fragments of abnormal alleles were all CAG repeats, which were 75 and 70, respectively. Conclusion CAG expansions were related to MJD. The technique of gene mutation detection can provide an effective way for the prediction of asymptomatic and genetic counseling, diagnosis and different diagnosis, which was fundamental for gene typing.更多还原