title: Parkin disease in a Brazilian kindred: Manifesting heterozygotes and clinical follow-up over 10 years.
abstract: We report on a large Brazilian kindred with young-onset parkinsonism due to either a homozygous or heterozygous mutation in parkin. A total of 6 members were affected: 5 were homozygous and 1 heterozygous for a deletion in exon 4. Two other heterozygotes also had extrapyramidal signs. All affected subjects showed characteristic features of parkin disease with foot dystonia and an excellent response to levodopa complicated by motor fluctuations and dyskinesia within 3 years of therapy. Careful clinical follow-up over 10 years showed the phenotype was similar in all the homozygotes with asymmetrical limb bradykinesia and early walking difficulties. Some acceleration of disability was observed in some of the cases as they entered the third decade of illness, but dementia was absent.
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, United Kingdom.
authors.forename: Naheed L
authors.initials: NL
authors.lastname: Khan
authors.affiliation: Hospital Universitario Walter Cantidio, Neurology Service and Movement Disorders Department, Federal University of Ceara, Fortaleza, Ceara, Brazil.
authors.forename: Wagner
authors.initials: W
authors.lastname: Horta
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Eunson
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Graham
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Janel O
authors.initials: JO
authors.lastname: Johnson
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, United Kingdom.
authors.forename: Mary
authors.initials: M
authors.lastname: Davis
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, United Kingdom.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, United Kingdom.|Reta Lila Weston Unit of Neurological Studies, Royal Free Hospital and University College Medical School, London, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
mesh_terms: D000328:Adult; D000978:Antiparkinson Agents / Q000009:adverse effects; D001938:Brazil; D004252:DNA Mutational Analysis; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005528:Foot / Q000503:physiopathology; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000208:ethnology* / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein