dc.contributor.advisor | Tekinay, Ayşe Begüm | |
dc.contributor.author | Ünal Gülsüner, Hilal | |
dc.date.accessioned | 2016-01-08T20:19:27Z | |
dc.date.available | 2016-01-08T20:19:27Z | |
dc.date.issued | 2015 | |
dc.identifier.uri | http://hdl.handle.net/11693/18450 | |
dc.description | Ankara : The Department of Materials Science and Nanotechnology and the Graduate School of Engineering and Science of Bilkent University, 2015. | en_US |
dc.description | Thesis (Ph. D) -- Bilkent University, 2015. | en_US |
dc.description | Includes bibliographical references leaves 74-84. | en_US |
dc.description.abstract | Neurodegenerative 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.statementofresponsibility | Gülsüner, Hilal Ünal | en_US |
dc.format.extent | xv, 98 leaves, illustrations, charts | en_US |
dc.language.iso | English | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Disease Gene İdentification | en_US |
dc.subject | Essential Tremor | en_US |
dc.subject | Hereditary Movement Disorders | en_US |
dc.subject | Mutation | en_US |
dc.subject | Next-Generation Sequencing | en_US |
dc.subject | Troyer Syndrome | en_US |
dc.subject.lcc | WL300 .G85 2015 | en_US |
dc.subject.lcsh | Tremor. | en_US |
dc.subject.lcsh | Essential tremor. | en_US |
dc.title | Genetics and mechanisms of essential tremor and related disorders | en_US |
dc.type | Thesis | en_US |
dc.department | Graduate Program in Materials Science and Nanotechnology | en_US |
dc.publisher | Bilkent University | en_US |
dc.description.degree | Ph.D. | en_US |
dc.identifier.itemid | B149456 | |
dc.embargo.release | 2017-01-19 | |