title: Defining the ends of Parkin exon 4 deletions in two different families with Parkinson's disease.
abstract: Autosomal recessive juvenile parkinsonism (AR-JP, PARK2) is characterized by an early onset parkinsonism, often presenting with dystonia as an early feature. Mutations in Parkin are a relatively common cause of AR-JP and are estimated to be present in approximately 30% of familial young onset Parkinson disease (PD) [Abbas et al. (1999); Hum Mol Genet 8:567-574]. These mutations include exon rearrangements (deletions and duplications), point mutations, and small deletions. Similar genomic mutations have been described in unrelated patients, thereby indicating independent mutational events or ancient founder effects. We have identified homozygous deletion mutations of exon 4 in Parkin in two unrelated families, one from Brazil and the other from Turkey [Dogu et al. (2004); Mov Dis 9:812-816; Khan et al., Mov Dis, in press]. We have performed molecular analysis of the deletion breakpoints and this data indicates these mutations originated independently. We present here data demonstrating that the mutation responsible for disease in the Brazilian kindred consists of two separate deletions (1,069 and 1,750 bp) surrounding and including exon 4. The deletion removing parkin exon 4 identified in the Turkish family extended 156,203 bp. In addition to demonstrating that disease in these families is not caused by a single founder mutation, these data show that there is no common fragile site between these mutational events.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. clarimon@mail.nih.gov
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimon
authors.forename: Janel
authors.initials: J
authors.lastname: Johnson
authors.forename: Okan
authors.initials: O
authors.lastname: Dogu
authors.forename: Wagner
authors.initials: W
authors.lastname: Horta
authors.forename: Naheed
authors.initials: N
authors.lastname: Khan
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
mesh_terms: D001483:Base Sequence; D001938:Brazil; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000235:genetics*; D014421:Turkey; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D004247:DNA; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein