Homozygous deletion mutation of the parkin gene in patients with atypical parkinsonism.
Autosomal recessive juvenile parkinsonism (AR-JP) is characterised by homogenous clinical features and selective degeneration of nigral neurons. Recent progress in molecular genetic analyses of AR-JP has led to the identification of a novel ubiquitin-like protein, parkin, whose precise function still remains to be elucidated. Two unrelated Japanese families had levodopa unresponsive parkinsonism complicated with cerebellar and pyramidal tract dysfunction. Genetic analysis of the parkin gene and mRNA in both families disclosed identical mutations with large deletions extending from exons 3 to 4. These results suggest that the parkin protein possesses an important function not only in the substantia nigra but also in extranigral neurons of the CNS and that the phenotype of multiple system dysfunction can also be a complication in patients with AR-JP due to variations in sites of or changes in functions by parkin mutation.
Kuroda
Y
Y
First Department of Internal Medicine, School of Medicine, The University of Tokushima, Kuramoto-3, Tokushima 770-8503, Japan.
Mitsui
T
T
Akaike
M
M
Azuma
H
H
Matsumoto
T
T
D015139:Blotting, Southern; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics*; D016133:Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases