The PD-linked mutations (A30P and A53T) were observed to affect both the morphology and the size distribution of alpha-synuclein protofibrils (measured by analytical ultracentrifugation and scanning transmission electron microscopy).
With these observations, we suggest that the A53T and A30P mutants may have different physiological consequences in vivo and could possibly contribute to early onset Parkinson's disease via unique mechanisms.
Although essentially all cases of sporadic and early-onset Parkinson's disease are of unknown etiology, two point mutations (A53T and A30P) in the alpha-synuclein gene have been identified in familial early-onset Parkinson's disease.
The results do not support a role for this mutation in our patients with early onset PD and, in agreement with the results previously reported, indicate that the Ala53Thr mutation of the alpha-synuclein gene is a rare cause of PD.