title: Early-onset Parkinson's disease associated with a new parkin mutation in a Spanish family.
abstract: Mutations in the PARKIN gene are associated with early-onset (juvenile) Parkinson's disease. We analyzed the coding sequence of this gene (exons 1-12) in patients from a family with three affected siblings, born to first-degree consanguineous parents, with an onset before 23 years and foot dystonia as the initial clinical symptom. The three patients were alive without cognitive impairment at ages of 70, 69, and 65 years, showing a marked response to levodopa treatment. A 2 bp-deletion at exon 11 (1276-1277 del GA) was found. The three patients were homozygous for this frameshift mutation, which would introduce a Stop at codon 394. This is a new PARKIN-mutation that would produce a truncated protein, lacking exon 12 and most the 11th. This region includes the C-terminal ring-finger domain of parkin, essential for its function as a ubiquitin-protein ligase. Compared to patients from other families with truncating mutations, our patients had an earlier onset. In addition, the three patients had dystonia at onset. In conclusion, we described a new PARKIN truncating mutation associated with an early onset parkinsonism, and the presence of foot dystonia as the initial symptom.
authors.affiliation: Genética Molecular, Hospital Central de Asturias, 33006 Oviedo, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Alvarez
authors.forename: L M
authors.initials: LM
authors.lastname: Guisasola
authors.forename: V G
authors.initials: VG
authors.lastname: Moreira
authors.forename: C H
authors.initials: CH
authors.lastname: Lahoz
authors.forename: E
authors.initials: E
authors.lastname: Coto
mesh_terms: D017668:Age of Onset; D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D010300:Parkinson Disease / Q000235:genetics*; D013030:Spain; D044767:Ubiquitin-Protein Ligases
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases