Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients
Identifieur interne : 001043 ( Main/Exploration ); précédent : 001042; suivant : 001044Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients
Auteurs : Denise M. Kay [États-Unis] ; Dawn Moran [États-Unis] ; Lina Moses [États-Unis] ; Parvoneh Poorkaj [États-Unis] ; Cyrus P. Zabetian [États-Unis] ; John Nutt [États-Unis] ; Stewart A. Factor [États-Unis] ; Chang-En Yu [États-Unis] ; Jennifer S. Montimurro [États-Unis] ; Robert G. Keefe [États-Unis] ; Gerard D. Schellenberg [États-Unis] ; Haydeh Payami [États-Unis]Source :
- Annals of Neurology [ 0364-5134 ] ; 2007-01.
Abstract
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
Url:
DOI: 10.1002/ana.21039
Affiliations:
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Zabetian</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Geriatric Research Education and Clinical Center, Veterans Administration Puget Sound Health Care System, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Department of Neurology, University of Washington School of Medicine, Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Nutt, John" sort="Nutt, John" uniqKey="Nutt J" first="John" last="Nutt">John Nutt</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Oregon</region></placeName><wicri:cityArea>Department of Neurology, Oregon Health and Science University, Portland</wicri:cityArea></affiliation></author><author><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A." last="Factor">Stewart A. Factor</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Géorgie (États-Unis)</region></placeName><wicri:cityArea>Department of Neurology, Emory University School of Medicine, Atlanta</wicri:cityArea></affiliation></author><author><name sortKey="Yu, Chang N" sort="Yu, Chang N" uniqKey="Yu C" first="Chang-En" last="Yu">Chang-En Yu</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Geriatric Research Education and Clinical Center, Veterans Administration Puget Sound Health Care System, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Montimurro, Jennifer S" sort="Montimurro, Jennifer S" uniqKey="Montimurro J" first="Jennifer S." last="Montimurro">Jennifer S. Montimurro</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Wadsworth Center, New York State Department of Health, Albany</wicri:cityArea></affiliation></author><author><name sortKey="Keefe, Robert G" sort="Keefe, Robert G" uniqKey="Keefe R" first="Robert G." last="Keefe">Robert G. Keefe</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Wadsworth Center, New York State Department of Health, Albany</wicri:cityArea></affiliation></author><author><name sortKey="Schellenberg, Gerard D" sort="Schellenberg, Gerard D" uniqKey="Schellenberg G" first="Gerard D." last="Schellenberg">Gerard D. Schellenberg</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Geriatric Research Education and Clinical Center, Veterans Administration Puget Sound Health Care System, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Washington (État)</region></placeName><wicri:cityArea>Departments of Neurology and Pharmacology, University of Washington, Seattle</wicri:cityArea></affiliation></author><author><name sortKey="Payami, Haydeh" sort="Payami, Haydeh" uniqKey="Payami H" first="Haydeh" last="Payami">Haydeh Payami</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Wadsworth Center, New York State Department of Health, Albany</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2007-01">2007-01</date><biblScope unit="volume">61</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="47">47</biblScope><biblScope unit="page" to="54">54</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">E3BC358056141E56C79051EF1E35EF32843F0DDF</idno><idno type="DOI">10.1002/ana.21039</idno><idno type="ArticleID">ANA21039</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Géorgie (États-Unis)</li><li>Oregon</li><li>Washington (État)</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Kay, Denise M" sort="Kay, Denise M" uniqKey="Kay D" first="Denise M." last="Kay">Denise M. Kay</name></region><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A." last="Factor">Stewart A. Factor</name><name sortKey="Factor, Stewart A" sort="Factor, Stewart A" uniqKey="Factor S" first="Stewart A." last="Factor">Stewart A. Factor</name><name sortKey="Keefe, Robert G" sort="Keefe, Robert G" uniqKey="Keefe R" first="Robert G." last="Keefe">Robert G. Keefe</name><name sortKey="Montimurro, Jennifer S" sort="Montimurro, Jennifer S" uniqKey="Montimurro J" first="Jennifer S." last="Montimurro">Jennifer S. Montimurro</name><name sortKey="Moran, Dawn" sort="Moran, Dawn" uniqKey="Moran D" first="Dawn" last="Moran">Dawn Moran</name><name sortKey="Moran, Dawn" sort="Moran, Dawn" uniqKey="Moran D" first="Dawn" last="Moran">Dawn Moran</name><name sortKey="Moses, Lina" sort="Moses, Lina" uniqKey="Moses L" first="Lina" last="Moses">Lina Moses</name><name sortKey="Nutt, John" sort="Nutt, John" uniqKey="Nutt J" first="John" last="Nutt">John Nutt</name><name sortKey="Payami, Haydeh" sort="Payami, Haydeh" uniqKey="Payami H" first="Haydeh" last="Payami">Haydeh Payami</name><name sortKey="Poorkaj, Parvoneh" sort="Poorkaj, Parvoneh" uniqKey="Poorkaj P" first="Parvoneh" last="Poorkaj">Parvoneh Poorkaj</name><name sortKey="Poorkaj, Parvoneh" sort="Poorkaj, Parvoneh" uniqKey="Poorkaj P" first="Parvoneh" last="Poorkaj">Parvoneh Poorkaj</name><name sortKey="Poorkaj, Parvoneh" sort="Poorkaj, Parvoneh" uniqKey="Poorkaj P" first="Parvoneh" last="Poorkaj">Parvoneh Poorkaj</name><name sortKey="Schellenberg, Gerard D" sort="Schellenberg, Gerard D" uniqKey="Schellenberg G" first="Gerard D." last="Schellenberg">Gerard D. Schellenberg</name><name sortKey="Schellenberg, Gerard D" sort="Schellenberg, Gerard D" uniqKey="Schellenberg G" first="Gerard D." last="Schellenberg">Gerard D. Schellenberg</name><name sortKey="Schellenberg, Gerard D" sort="Schellenberg, Gerard D" uniqKey="Schellenberg G" first="Gerard D." last="Schellenberg">Gerard D. Schellenberg</name><name sortKey="Yu, Chang N" sort="Yu, Chang N" uniqKey="Yu C" first="Chang-En" last="Yu">Chang-En Yu</name><name sortKey="Yu, Chang N" sort="Yu, Chang N" uniqKey="Yu C" first="Chang-En" last="Yu">Chang-En Yu</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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