Mutation analysis of the parkin gene in Russian families with autosomal recessive juvenile parkinsonism.

Autosomal recessive juvenile parkinsonism (AR-JP) is a form of hereditary parkinsonism characterized by variable clinical presentations and caused by mutations in a novel gene, parkin, on chromosome 6q25.2-27. Until now, no Russian cases of parkin-associated AR-JP have been reported on. We recruited 16 patients from 11 Russian families with dopa-responsive movement disorders according to the following criteria: 1) family history compatible with autosomal recessive inheritance; 2) onset of symptoms at </=30 years of age; and 3) the lack of mutations in the GTP cyclohydrolase I gene (in sporadic cases). Mutation screening of the parkin gene was carried out by a semiquantitative PCR assay and direct sequencing of the coding region. Six different parkin mutations (both deletions and point mutations) were identified in the index cases from four families, including a novel point mutation in the donor splice site (IVS1+1G-->A). The majority of our parkin-associated cases were characterized by early-onset dopa-responsive parkinsonism with benign course and slow progression (5 patients from two families have been followed for as long as 18-36 years), and 1 patient had a phenotype of dopa-responsive dystonia. This first description of Russian patients with AR-JP and molecularly proven parkin mutations confirms the widespread occurrence of this polymorphic hereditary extrapyramidal disorder.