Parkin-proven disease: common founders but divergent phenotypes.


Journal Article

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.Clinical review, parkin gene sequencing, dosage studies, and high-resolution genotype/haplotype analysis were performed.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.Parkin mutations on common parkin haplotypes provide testable hypotheses of parkin function in genetically defined parkinsonism.

Full Text

Duke Authors

Cited Authors

  • Lincoln, S; Wiley, J; Lynch, T; Langston, JW; Chen, R; Lang, A; Rogaeva, E; Sa, DS; Munhoz, RP; Harris, J; Marder, K; Klein, C; Bisceglio, G; Hussey, J; West, A; Hulihan, M; Hardy, J; Farrer, M

Published Date

  • May 2003

Published In

Volume / Issue

  • 60 / 10

Start / End Page

  • 1605 - 1610

PubMed ID

  • 12771249

Pubmed Central ID

  • 12771249

Electronic International Standard Serial Number (EISSN)

  • 1526-632X

International Standard Serial Number (ISSN)

  • 0028-3878

Digital Object Identifier (DOI)

  • 10.1212/01.wnl.0000064289.49410.a9


  • eng