TY - JOUR
T1 - parkin mutation dosage and the phenomenon of anticipation
T2 - A molecular genetic study of familial parkinsonism
AU - Poorkaj, Parvoneh
AU - Moses, Lina
AU - Montimurro, Jennifer S.
AU - Nutt, John G.
AU - Schellenberg, Gerard D.
AU - Payami, Haydeh
PY - 2005/2/22
Y1 - 2005/2/22
N2 - 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 lateonset 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 ≥ 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.
AB - 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 lateonset 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 ≥ 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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U2 - 10.1186/1471-2377-5-4
DO - 10.1186/1471-2377-5-4
M3 - Article
C2 - 15725358
AN - SCOPUS:23344448961
SN - 1471-2377
VL - 5
JO - BMC Neurology
JF - BMC Neurology
M1 - 4
ER -