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Mutation analysis of the parkin gene in Russian families with autosomal recessive juvenile parkinsonism
Author(s) -
Illarioshkin Sergei N.,
Periquet Magali,
Rawal Nina,
Lücking Christoph B.,
Zagorovskaya Tatyana B.,
Slominsky Pyotr A.,
Miloserdova Olga V.,
Markova Elena D.,
Limborska Svetlana A.,
IvanovaSmolenskaya Irina A.,
Brice Alexis
Publication year - 2003
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.10467
Subject(s) - parkin , parkinsonism , genetics , point mutation , dystonia , gtp cyclohydrolase i , mutation , biology , gene , medicine , parkinson's disease , disease , endocrinology , neuroscience , tetrahydrobiopterin , nitric oxide synthase , nitric oxide
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. © 2003 Movement Disorder Society