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Letters |

Identifying Genetic Factors in Parkinson Disease

Matt Farrer, PhD; John Hardy, PhD; Mike Hutton, PhD; Demetrius Maraganore, MD; Yoshio Tsuboi, MD; Zbigniew K. Wszolek, MD
JAMA. 2002;287(6):715-716. doi:10.1001/jama.287.6.711.
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To the Editor: Dr Martin and colleagues1 found that the tau gene is associated with late-onset Parkinson disease (PD). In a related study by the same group, Dr Scott and colleagues2 found that the parkin gene may be associated with idiopathic PD. The syndrome "parkinsonism" includes several complex and multigenic disorders, with many loci linked to Lewy body pathology and many others linked to other pathologic substrates. However, while it seems clear that the tau H1 haplotype is associated with late-onset parkinsonism (and presumably PD), the increase in risk is relatively low (odds ratios, 1.05-1.3) and less than that seen in progressive supranuclear palsy.3 It is unlikely that such small increases in risk could be identified in a genome screen paradigm and indeed it was not detected in a recent genome screen of comparable power.4 However, many families with frontal temporal dementia and tau mutations have pronounced parkinsonism,5 although some have tau pathology at autopsy.6 It would seem prudent to sequence the tau gene in families in which the tau locus is coinherited with disease to determine whether these families carry such mutations.

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