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Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients
Author(s) -
Kay Denise M.,
Moran Dawn,
Moses Lina,
Poorkaj Parvoneh,
Zabetian Cyrus P.,
Nutt John,
Factor Stewart A.,
Yu ChangEn,
Montimurro Jennifer S.,
Keefe Robert G.,
Schellenberg Gerard D.,
Payami Haydeh
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21039
Subject(s) - parkin , genetics , compound heterozygosity , mutation , parkinsonism , parkinson's disease , point mutation , case control study , disease , medicine , biology , gene
Objective Homozygous or compound heterozygous parkin mutations cause juvenile parkinsonism. Heterozygous parkin mutations are also found in patients with typical Parkinson's disease (PD), but it is unclear whether a single “mutation” in a patient is related to disease or is coincidental, because the mutation frequency in control subjects is unknown. We present a comprehensive sequence analysis of parkin in control subjects. Methods A total of 302 patients and 301 control subjects were sequenced, and findings were replicated in 1,260 additional patients and 1,657 control subjects. Results Thirty‐four variants were detected, of which 21 were novel; 12 were polymorphisms and 22 were rare variants. Patients and control subjects did not differ in the frequency, type, or functional location of the variants. Even P437L, a common mutation thought to be pathogenic, was present in unaffected control subjects. Interpretation parkin point mutations are not exclusive to PD. The mere presence of a single point mutation in a patient, in the absence of a second mutation, should not be taken as a cause of disease unless corroborated by family data and functional studies. This study does not support the notion that heterozygous parkin sequence variants (mutations or polymorphisms) are risk factors for PD. Whether heterozygous dosage anomalies are associated with PD remains to be determined. Ann Neurol 2006