三核苷酸重复的检测在脊髓小脑型共济失调的应用研究

Detection of trinucleotide repeat expansions in the study of hereditary spinocerebellar ataxia (SCA) and its clinical significance

目的建立中国人遗传性脊髓小脑型共济失调（ＳＣＡ）患者的ＳＣＡ１、ＳＣＡ２、ＳＣＡ３／ＭＪＤ、ＳＣＡ６型的ＣＡＧ三核苷酸重复（ＣＡＧ）ｎ频率的检测方法并探讨其诊断意义。方法应用聚合酶链式反应（ＰＣＲ）和６％变性聚丙烯酰胺凝胶电泳技术，检测了３０例正常人和６例临床诊断为ＳＣＡ患者上述４型的（ＣＡＧ）ｎ重复数。结果３０例正常人（ＣＡＧ）ｎ的重复数目分别为ＳＣＡ１６～４０次，ＳＣＡ２２２～２９次，ＳＣＡ３１３～３６次，ＳＣＡ６４～１６次。６例ＳＣＡ患者中２例有ＳＣＡ３异常，（ＣＡＧ）ｎ重复数分别为６７和７５，而ＳＣＡ１、ＳＣＡ２、ＳＣＡ６型（ＣＡＧ）ｎ重复数均在正常范围内。结论研究三核苷酸重复频率的检测为ＳＣＡ患者提供了准确可靠的诊断方法和标准。

Objective To establish the detective methods of the frequence of the SCA 1, SCA 2, SCA 3/MJD,SCA 6 type CAG trinucleotide repeat expansions (CAG)n among Chinese patients with hereditary spinocerebeller ataxia (SCA) and discuss its clinical significance. Method The (CAG)n mutations of SCA 1.2.3.6 were detected with polymerase chain reaction(PCR) and analyzed by 6% denaturing polyacrylamie gel in 30 controls and 6 patients with SCA by clinical findings. Results Among 30 normal people the (CAG)n repeats of each type were:SCA 1,6～40 repeats,SCA 2 22～29 repeats,SCA 3 13～36 repeats,SCA 6 4～16 repeats.2 cases of 6 presumed SCA patients had abnormal SCA 3,(CAG)n repeats:67 and 75 respectively.The (CAG)n repeats of SCA 1,SCA 2 and SCA 6 were all normal.Conclusion The method introduced in the paper is reliable.The results are accurate and can be used as diagnostic criteria.