Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
BMC Neurol. 2005 Feb 22;5(1):4.

Parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism.

Author information

  • 1Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA. pips@u.washington.edu

Abstract

BACKGROUND:

parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage.

METHODS:

We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and > or = 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons.

RESULTS:

Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations.

CONCLUSION:

Anticipation is not linked to parkin, and may signify a distinct disease entity.

PMID:
15725358
[PubMed - indexed for MEDLINE]
PMCID:
PMC551608
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk