Analysis And Application Of Spinocerebellar Ataxia Type 1,2,3 Gene And Mitochondrial DNA Partly Mutations In SCA1,SCA2,SCA3

Objective:Analysis and application of spinocerebellar ataxia type 1,2,3,7(SCA1,2,3,7) gene and the possible relationship between mitochondrial DNA (mtDNA) and SCA1,SCA2,SCA3.Methods:1.The part one of this study included 119 patients and their relatives with autosomal dominant SCA from 18 kindreds and 12 sporadic SCA patients.Fluorescence-PCR and fragment analysis with capillary electrophoresis were applied to count the CAG-repeat expansion of SCA1,2,3,7 gene and was proved with sequencing.2.Polymerase chain reaction(PCR) was used to amplify 10 mtDNA segments of 48 patients and presymptomatic individuals, 84volunteers.The 10 mtDNA segments are closely related to respiratory chain respectively,these are gene ND1,ND2,ND3,ND4,ND5,CO1,CO2,CO3,NC7lied in.For PCR products of above fragments,single strand conformation polymorphism(SSCP) was executed to detect mutations and the abnormal segments were sequenced.Results:1.5 patients,presymptomatic relatives and 1 sporadic patient were confirmed by detecting the presence of abnormal CAG-repeat expansion in SCA1 gene.2 patients and presymptomatic relatives were confirmed by detecting the presence of abnormal CAG-repeat expansion in SCA2 gene.48 patients,presymptomatic relatives and 4 sporadic patients were confirmed by detecting the presence of abnormal CAG-repeat expansion in SCA3 gene.2.A new mtDNA mutation in segments of mtDNA point 11893(A＞G),was identified in 3 SCA1 members.A deletion mutation in segments of point 8282-8290,was identified in 4 SCA3 members.A new mtDNA mutation in segments of mtDNA point 13731(T＞C),was identified in another 3 SCA3 members.3.A classics mtDNA mutation in segments of mtDNA point 5460(A＞G), was identified in 41 SCA genealogical members and 4 SCA sporadic patients, The frequency was also significantly higher than the control group(X ~2=39.928,P＜0.01).But,there were no significant differences between the 3 genictypes(X~2=1.556,P＞0.5).Conclusion:We can made genetic diagnosis of SCA1,SCA2,SCA3by detecting the CAG-repeat expansion of SCA1,SCA2,SCA3gene.The frequcncy of SCA3 is substantially higher than that of SCA1 and SCA2 in the autosomal dom inant SCA patients;SCA7 are rare srbtyps.These mutations of mtDNA may be related to SCA.