Genetics and mechanisms of essential tremor and related disorders

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buir.advisorTekinay, Ayşe Begüm
dc.contributor.authorÜnal Gülsüner, Hilal
dc.date.accessioned2016-01-08T20:19:27Z
dc.date.available2016-01-08T20:19:27Z
dc.date.issued2015
dc.departmentGraduate Program in Materials Science and Nanotechnologyen_US
dc.descriptionAnkara : The Department of Materials Science and Nanotechnology and the Graduate School of Engineering and Science of Bilkent University, 2015.en_US
dc.descriptionThesis (Ph. D) -- Bilkent University, 2015.en_US
dc.descriptionIncludes bibliographical references leaves 74-84.en_US
dc.description.abstractNeurodegenerative disorders are characterized by progressive nervous system dysfunction, and they remain as one of the most challenging disorders known to humankind. These disorders have devastating effects on patients and currently there are no effective therapeutic approaches. Approved medicines provide only symptomatic relief, and inadequacy of information about the molecular mechanisms underlying these conditions restricts the development of new effective therapies. In this thesis, I presented the genetic analysis of two different neurodegenerative disorders and investigate the molecular mechanisms underlying these two disorders: essential tremor and Troyer syndrome. Essential tremor is one of the most prevalent movement disorders; however, its genetic cause and molecular mechanisms remain unknown because of its clinical heterogeneity, age-dependent penetrance, variable expressivity, and relation to other neurodegenerative disorders. In a six-generation consanguineous Turkish family with both essential tremor and Parkinson’s disease, we identified a rare missense mutation of HTRA2 as the causative allele. Family members homozygous for this allele were more severely affected than those heterozygous for this allele. Troyer syndrome is a very rare autosomal recessive neurodegenerative disorder with only several described cases. Only two reports with truncating mutations have been described. In a consanguineous Turkish kindred with two affected siblings presenting tremor of the hands as well as clinical features similar to that of Troyer syndrome, we identified a novel missense mutation in SPG20. We presented a genotype-phenotype correlation in this family, and the missense SPG20 p.G580R mutation was found to result in a milder form of Troyer syndrome without skeletal abnormalities. Overall, this study provides solutions to complexities of neurodegenerative disorders by suggesting a novel and unifying molecular mechanism underlying essential tremor and Parkinson’s disease. Furthermore, correlation of genotypes and phenotypic differences in patients with Troyer syndrome explains the clinical heterogeneity and variable expressivity of neurodegenerative disorders.en_US
dc.description.degreePh.D.en_US
dc.description.statementofresponsibilityGülsüner, Hilal Ünalen_US
dc.embargo.release2017-01-19
dc.format.extentxv, 98 leaves, illustrations, chartsen_US
dc.identifier.itemidB149456
dc.identifier.urihttp://hdl.handle.net/11693/18450
dc.language.isoEnglishen_US
dc.publisherBilkent Universityen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectDisease Gene İdentificationen_US
dc.subjectEssential Tremoren_US
dc.subjectHereditary Movement Disordersen_US
dc.subjectMutationen_US
dc.subjectNext-Generation Sequencingen_US
dc.subjectTroyer Syndromeen_US
dc.subject.lccWL300 .G85 2015en_US
dc.subject.lcshTremor.en_US
dc.subject.lcshEssential tremor.en_US
dc.titleGenetics and mechanisms of essential tremor and related disordersen_US
dc.typeThesisen_US

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Graduate Program in Materials Science and Nanotechnology - Ph.D. / Sc.D.