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. 2005 Feb 22;5(1):4.
doi: 10.1186/1471-2377-5-4.

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

Parvoneh Poorkaj  1 , Lina Moses, Jennifer S Montimurro, John G Nutt, Gerard D Schellenberg, Haydeh Payami
Affiliations

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

Parvoneh Poorkaj et al. BMC Neurol. .

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.

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