title: Mutation analysis of the parkin gene in Russian families with autosomal recessive juvenile parkinsonism.
abstract: 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.
authors.affiliation: Department of Neurogenetics, Institute of Neurology, Russian Academy of Medical Sciences, Moscow, Russia. s-illario@mtu-net.ru
authors.forename: Sergei N
authors.initials: SN
authors.lastname: Illarioshkin
authors.forename: Magali
authors.initials: M
authors.lastname: Periquet
authors.forename: Nina
authors.initials: N
authors.lastname: Rawal
authors.forename: Christoph B
authors.initials: CB
authors.lastname: Lücking
authors.forename: Tatyana B
authors.initials: TB
authors.lastname: Zagorovskaya
authors.forename: Pyotr A
authors.initials: PA
authors.lastname: Slominsky
authors.forename: Olga V
authors.initials: OV
authors.lastname: Miloserdova
authors.forename: Elena D
authors.initials: ED
authors.lastname: Markova
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Limborska
authors.forename: Irina A
authors.initials: IA
authors.lastname: Ivanova-Smolenskaya
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000328:Adult; D000978:Antiparkinson Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D006136:GTP Cyclohydrolase / Q000235:genetics; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000208:ethnology* / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D012720:Severity of Illness Index; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D006136:GTP Cyclohydrolase