Browsing by Subject "Pachygyria"
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Item Open Access Genetic influences on cortical structure and function(Bilkent University, 2018-07) Demirayak, PınarStructure and function of the human central nervous system is determined by both genetic and environmental in uences. One of the fundamental quests in neuroscience studies is to determine to what degree each of these two factors in uence the development and function of the nervous system and, ultimately, human behavior. However, this is an inherently di cult problem to tackle as it is nearly impossible to tease apart the individual contributions of genes and environment, since they interact heavily throughout an organism's life. Recently, our understanding about the role that speci c genes play in the development of brain structure and function, has been greatly advanced by studies that combine genetic and neuroimaging methods to investigate congenital neurodevelopmental disorders. These studies of patients, that are homozygous for a speci c mutation, allow to single out contributions of individual genes in the neurodevelopmental process and have the potential to reveal gene-based alterations in cortical structure and function that can not be compensated by mechanisms of cortical plasticity or mitigating environmental e ects. In this thesis I pursue this promising approach further and investigate the e ects of three di erent single gene mutations on brain structure and function - namely RAD51, LAMC3 and HTRA2. Each of these genes is highly expressed during neurodevelopment, and each in uences cortical structure and function di erently. Overall, I nd that these genes are all highly associated with abnormal structural and functional connectivity patterns, however, and surprisingly, highly abnormal structure does not necessarily predict highly abnormal behavior.Item Open Access Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy(Springer, 2010) Kolb, L. E.; Arlier, Z.; Yalcinkaya, C.; Ozturk, A. K.; Moliterno, J. A.; Erturk, O.; Bayrakli, F.; Korkmaz, B.; DiLuna, M. L.; Yasuno, K.; Bilguvar, K.; Ozcelik, T.; Tuysuz, B.; State, M. W.; Gunel, M.Congenital ataxia with cerebellar hypoplasia is a heterogeneous group of disorders that presents with motor disability, hypotonia, incoordination, and impaired motor development. Among these, disequilibrium syndrome describes a constellation of findings including non-progressive cerebellar ataxia, mental retardation, and cerebellar hypoplasia following an autosomal recessive pattern of inheritance and can be caused by mutations in the Very Low Density Lipoprotein Receptor (VLDLR). Interestingly, while the majority of patients with VLDL-associated cerebellar hypoplasia in the literature use bipedal gait, the previously reported patients of Turkish decent have demonstrated similar neurological sequelae, but rely on quadrupedal gait. We present a consanguinous Turkish family with two siblings with cerebellar atrophy, predominantly frontal pachygyria and ataxic bipedal gait, who were found to have a novel homozygous deletion in the VLDLR gene identified by using high-density single nucleotide polymorphism microarrays for homozygosity mapping and identification of CNVs within these regions. Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia.