The Study Of Genetic Diagnosis And Mitochondrial DNA Partly Mutations In Spinocerebellar Ataxia Type 3

Objective: To study the genetic diagnosis of spinocerebellar ataxia type 3 (SCA3) and the possible relationship between mitochondrial DNA (mtDNA) and SCA3.Methods: 1. The part one of this study included 92 patients and their relatives with autosomal dominant SCA from 10 kindreds and 11 sporadic SCA patients. Fluorescence-PCR and fragment analysis with capillary electrophoresis was applied to count the CAG-repeat expansion of MJD1 gene and was proved with sequencing.2.Polymerase chain reaction (PCR) was used to amplify 2 mtDNA segments of 43 patients and presymptomatic individuals , 30 volunteers. The point 8344 and 11893 lied in the above 2 mtDNA segments respectively. For PCR products of point 8344 and 11893, single strand conformation polymorphism (SSCP) was executed to detect mutations and the abnormal segments were sequenced.Results: 1. 43 patients and presymptomatic relatives were confirmed by detecting the presence of abnormal CAG-repeat expansion in MJD1 gene.2.We had not found mutation in the segments point 11893 lied in. However,a new mtDNA mutation, deletion mutation in segments of point 8344,was identified in 1 patient and 3 presymptomatic relatives.Conclusion: We can made genetic diagnosis of SCA3 by detecting the CAG-repeat expansion of MJD1 gene. Although CAG copies influence on disease phenotype , it could not be made as the only predictable index of clinical features. The new deletion mutation of mtDNA may be related to SCA3.