MN SOD ACTIVITY AND PROTEIN IN A PATIENT WITH CHROMOSOME 6-LINKED AUTOSOMAL RECESSIVE PARKINSONISM IN COMPARISON WITH PARKINSONS-DISEASE AND CONTROL

We report Mn superoxide dismutase (SOD) protein and activity in a pati ent with familial autosomal recessive Lewy body-negative parkinsonism in comparison with patients with sporadic Parkinson's disease (PD) and controls. We recently proved linkage of this family with markers of c hromosome 6 at 6q25.2-27, which included the Mn SOD gene. We used a no vel polymorphic mutation at -9 position of the signal peptide of the M n SOD precursor protein, which caused valine to alanine substitution. All the affected members of this family showed homozygosity for alanin e, whereas nonaffected members, sporadic PD patients, and the control subjects studied showed either heterozygosity of alanine and valine or homozygosity of valine. The Mn SOD activity of this familial patient was the highest among the PD patients and the control subjects studied , and an abundant expression of Mn SOD was found in the substantia nig ra. The molecular weight of Mn SOD protein by Western blotting of this patient was essentially similar to that of PD patients and the contro l subjects. High Mn SOD activity may constitute a genetic risk factor in this familial patient. The difference in the signal peptide sequenc e may affect the expression of Mn SOD within mitochondria; however, it is unlikely that loss of function type Mn SOD mutation is the cause o f this familial parkinsonism. Mn SOD in sporadic PD patients was simil ar to that in controls.