Mutations of mitochondrial genome in spinocerebellar degeneration

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Spinocerebellar degeneration represents a group of heterogeneous degenerative diseases showing ataxia as the main symptom. This disorder is clinically characterized by slowly progressive course,and various combinations of signs and symptoms of the pyramidal and extrapyramidal tracts and the peripheral nervous system. In order to investigate the possible role of mitochondrial dysfunction in the pathogenesis of extensive neuronal degeneration in this disorder,we have analyzed the mutations of mitochondrial DNA in patients with spinocerebellar degeneration. Mitochondrial DNA(mtDNA)was amplified by the polymerase chain reaction (PCR)from DNA isolated from platelets of each patient.The single strand DNA was amplified from the first PCR product by using the asymmetric PCR method. The second PCR product was used as the template for the fluorescence-based direct PCR sequencing. Sequences of these mtDNA fragments were analyzed by an automated DNA sequencer. In 43 cases of spinocerebellar degene … More ration,sequence analysis and restriction fragment analysis revealed neither the 8344 A-to-G nucleotide substitution reported in patients with MERRF syndrome nor the 8993 G-to-T transversion reported in a patient with cerebellar ataxia,retinitis pigmentosa, and cardiomyopathy. Sequence analysis of the whole mtDNA from two patients whose family histories were consistent with maternal inheritance revealed multiple mutations in the non-coding regions,rRNA genes,and mRNA genes. Although some of these mutations in these two patients were also observed in other disease and normal controls,several nonsynonymous mutations in Patient 2 were not found in the normal controls. Both of the mutations in the ND2 and ATP6 genes in Patient 2 were also found in a paient with Parkinson's disease as well as in Control 1,who died at the age of 55 from gastric cancer. The possible involvement of these mutations in the pathogenesis of spinocerebellar degeneration must be evaluated from further study on the sequence heterogeneity of mtDNA among normal controls as well as disease controls. Less