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dc.contributor.authorGulumser, H. U.en_US
dc.contributor.authorGulsuner, S.en_US
dc.contributor.authorMercan, F. N.en_US
dc.contributor.authorOnat, O. E.en_US
dc.contributor.authorWalsh, T.en_US
dc.contributor.authorShahin, H.en_US
dc.contributor.authorLee, M. K.en_US
dc.contributor.authorDogu, O.en_US
dc.contributor.authorKansu, T.en_US
dc.contributor.authorTopaloglu, H.en_US
dc.contributor.authorElibol, B.en_US
dc.contributor.authorAkbostanci, C.en_US
dc.contributor.authorKing, M. C.en_US
dc.contributor.authorOzcelik, T.en_US
dc.contributor.authorTekinay, A. B.en_US
dc.date.accessioned2015-07-28T12:02:11Z
dc.date.available2015-07-28T12:02:11Z
dc.date.issued2014-12-23en_US
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/11693/12611
dc.description.abstractEssential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.en_US
dc.language.isoEnglishen_US
dc.source.titleProceedings of the National Academy of Sciencesen_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1419581111en_US
dc.titleMitochondrial serine protease HTRA2 p.G3999S in a kindred with essential tremor and Parkinson diseaseen_US
dc.typeArticleen_US
dc.departmentInstitute of Materials Science and Nanotechnologyen_US
dc.citation.spage18285en_US
dc.citation.epage18290en_US
dc.citation.volumeNumber111en_US
dc.citation.issueNumber51en_US
dc.instituteInstitute of Materials Science and Nanotechnologyen_US
dc.identifier.doi10.1073/pnas.1419581111en_US
dc.publisherNational Academy of Sciencesen_US
dc.identifier.eissn1091-6490


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