Browsing by Author "Dundar, M"

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    Autozygosity in a Turkish family with scoliosis, blindness, and arachnodactyly syndrome
    Orenay-Boyacioglu, S; Tekin, M; Dundar, M
    BACKGROUND AND OBJECTIVES: Blindness-scoliosis-arachnodactyly syndrome has been described in a family with parental consanguinity. We present the strategy employed to determine the gene locus responsible for the syndrome. DESIGN AND SETTING: A retrospective study of blindness-scoliosis-arachnodactyly syndrome patients at the Department of Medical Genetics, Erciyes University, between 2009-2010. PATIENTS AND METHODS: Whole genome single nucleotide polymorphisms (SNPs) were scanned using a 250K Affymetrix array. We visually evaluated runs of homozygosity shared by two affected brothers that segregated in the entire pedigree with different combinations due to the unclear affected status of some siblings. Two and multiple-point LOD (logarithm [base 10] of odds) score analyses were performed by easyLINKAGEplus v5.08. RESULTS: Five homozygous blocks over 2 Mb shared by two affected brothers segregated with phenotype in two affected and three unaffected siblings and in the mother whose phenotypes were unequivocal. The longest homozygous block in this analysis was on chromosome 14 between 67817621bp (rs7148416) and 82508151bp (rs17117757). When another sister with positive eye findings was added to the analysis, this region was narrowed to between 67817621bp (rs7148416) and 75657598bp (rs11626830), with a maximum LOD score of 2.3956 by two-point analysis. Three candidate genes were detected in this region. CONCLUSION: This study contributes to the existing literature on the region 67817621 bp 82508151 bp (rs17117757) on chromosome 14 and the three candidate genes, which could be responsible for the syndrome.
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    Epigenetic analysis of heat shock activator complex in the peripheral blood of Parkinson's disease patients and its clinical significance
    Gemici, YI; Tasci, I; Dundar, M; Ozgen, N; Danis, N; Gozukara, HG; Koc, A
    Objectives: This study aimed to investigate the methylation changes of related genes in the peripheral blood and their clinical significance in Parkinson's disease (PD) and whether the methylation change of the gene encoding long noncoding RNA was different in the blood of patients and controls. Patients and methods: This prospective cross-sectional, controlled study was conducted with 45 participants (22 males, 23 females; mean age: 60.7 +/- 5.9 years; range, 53 to 75 years) between June 2020 and June 2021. Drug-naive patients diagnosed with PD were included in this study. Those with PD and a Mini-Mental State Examination (MMSE) score >23 were defined as Group 1 (n=15), and those with PD and an MMSE score <= 23 were defined as Group 2 (n=15). Controls were included in Group 3 (n=15). The methylation changes of genes HSP70, HSP90, heat shock factor 1 (HSF1), heat shock RNA 1 (HSR1), and eukaryotic translation elongation factor 1 alpha (eEF1a) a ) were investigated with methylation-specific real-time quantitative polymerase chain reaction analysis. Results: The eEF1a a was significantly more hypermethylated in Group 1. In Group 2, HSP70, HSP90 HSF1, HSR1, and eEF1a a were significantly hypomethylated compared to Group 1 and Group 3 (for all genes p<0.001). The HSF1 hypomethylation was negatively correlated with MMSE and positively correlated with depression scores (p=0.03 and p=0.013, respectively). The correlation of eEF1a a with MMSE and depression was the opposite of HSF1 (p<0.001 and p=0.013, respectively). Conclusion: Cell line and autopsy studies indicate that eEF1a a hypermethylation might be one of the main molecules triggering alpha-synuclein aggregation in the pathogenesis of PD. Therefore, eEF1a a may be a molecule that can be used as a peripheral biomarker. The findings supported this idea as it was more hypermethylated in PD patients than in controls, whereas its negative regulator HSF1 was hypomethylated and correlated with the clinic. Furthermore, the worsening of cognitive functions and depression in PD patients may affect methylation levels of chaperone genes in the peripheral blood.
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    Germline landscape of BRCAs by 7-site collaborations as a BRCA consortium in Turkey
    Bisgin, A; Sag, SO; Dogan, ME; Yildirim, MS; Gumus, AA; Akkus, N; Balasar, O; Durmaz, CD; Eroz, R; Altiner, S; Alemdar, A; Aliyeva, L; Boga, I; Cam, FS; Dorgan, B; Esbah, O; Hanta, A; Mujde, C; Ornek, C; Ozer, S; Rencuzogullari, C; Sonmezler, O; Bozdogan, ST; Dundar, M; Temel, SG
    BRCA1/2 mutations play a significant role in cancer pathogenesis and predisposition particularly in breast, ovarian and prostate cancers. Thus, germline analysis of BRCA1 and BRCA2 is essential for clinical management strategies aiming at the identification of recurrent and novel mutations that could be used as a first screening approach. We analyzed germline variants of BRCA1/2 genes for 2168 individuals who had cancer diagnosis or high risk assessment due to BRCAs related cancers, referred to 10 health care centers distributed across 7 regions covering the Turkish landscape. Overall, 68 and 157 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-two novel variants were reported from both genes while BRCA2 showed higher mutational heterogeneity. We herein report the collective data as BRCA Turkish consortium that confirm the molecular heterogeneity in BRCAs among Turkish population, and also as the first study presenting the both geographical, demographical and gene based landscape of all recurrent and novel mutations which some might be a founder effect in comparison to global databases. This wider perspective leads to the most accurate variant interpretations which pave the way for the more precise and efficient management affecting the clinical and molecular aspects.