Parkin Mutations (Park 2)

Publisher Summary Park2 (autosomal recessive-juvenile parkinsonism (AR-JP)) presents young-onset parkinsonism, consisting of gait disturbance, rest tremor, cogwheel rigidity, and bradykinesia. Clinical features are essentially similar to those of late-onset sporadic Parkinson's disease. They respond to levodopa well. Progression is slow. Pathologic features include extensive nigral and locus coeruleus degeneration and gliosis without Lewy body formation. The disease gene is identified and named parkin, which is located on the long arm of chromosome 6 at 6q25-27.2. Varieties of deletion mutations and point mutations of parkin are found in patients with Park2. Compound heterozygotes are also found. Parkin protein functions as a ubiquitin ligase and a number of candidate substrates for Parkin are reported including CDCrel 1, α-synuclein 22, Pael receptor, synphilin-1, and CDCrel 2A. Accumulation of one or more of the candidate substrates appears to be the cause of nigral degeneration. Park2 is considered to represent the most common form of familial Parkinson's disease.