title: Parkin-proven disease: common founders but divergent phenotypes.
abstract: OBJECTIVE
  To compare and contrast clinical and genetic findings in six probands with parkinsonism with a parkin exon 3 438- to 477-bp deletion (Ex3Delta40) to search for evidence of a common founder.
  
  
  METHODS
  Clinical review, parkin gene sequencing, dosage studies, and high-resolution genotype/haplotype analysis were performed.
  
  
  RESULTS
  All subjects had two or more signs consistent with a diagnosis of possible or probable PD with age at onset younger than 45 years (mean +/- SD 29.3 +/- 10.2 years, range 16 to 42 years). Affected individuals were either homozygotes, compound heterozygotes, or Ex3Delta40 carriers with one normal parkin allele. Haplotype analysis revealed both Ex3Delta40 and Ex7 924 C-->T (R275W) mutations originated from common founders, the former most probably of Irish descent. Although three cases had Ex7 924 C-->T (R275W) and Ex3Delta40 mutations, their clinical presentation and mode of inheritance were variable.
  
  
  CONCLUSIONS
  Parkin mutations on common parkin haplotypes provide testable hypotheses of parkin function in genetically defined parkinsonism.
authors.affiliation: Neurogenetic Laboratories, Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lincoln
authors.forename: J
authors.initials: J
authors.lastname: Wiley
authors.forename: T
authors.initials: T
authors.lastname: Lynch
authors.forename: J W
authors.initials: JW
authors.lastname: Langston
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Lang
authors.forename: E
authors.initials: E
authors.lastname: Rogaeva
authors.forename: D S
authors.initials: DS
authors.lastname: Sa
authors.forename: R P
authors.initials: RP
authors.lastname: Munhoz
authors.forename: J
authors.initials: J
authors.lastname: Harris
authors.forename: K
authors.initials: K
authors.lastname: Marder
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: G
authors.initials: G
authors.lastname: Bisceglio
authors.forename: J
authors.initials: J
authors.lastname: Hussey
authors.forename: A
authors.initials: A
authors.lastname: West
authors.forename: M
authors.initials: M
authors.lastname: Hulihan
authors.forename: J
authors.initials: J
authors.lastname: Hardy
authors.forename: M
authors.initials: M
authors.lastname: Farrer
mesh_terms: D000328:Adult; D005091:Exons / Q000235:genetics; D005260:Female; D018703:Founder Effect; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein