Browsing by Author "Temel, SG"

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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.
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    Identification and characterization of a novel FBN1 gene variant in an extended family with variable clinical phenotype of Marfan syndrome
    Ergoren, MC; Turkgenc, B; Terali, K; Rodoplu, O; Verstraeten, A; Van Laer, L; Mocan, G; Loeys, B; Tetik, O; Temel, SG
    Marfan syndrome (MFS) is a multi-systemic autosomal dominant condition caused by mutations in the gene (FBN1) coding for fibrillin-1. Mutations have been associated with a wide range of overlapping phenotypes. Here, we report on an extended family presenting with skeletal, ocular and cardiovascular clinical features. The 37-year-old male propositus, who had chest pain, dyspnea and shortness of breath, was first diagnosed based on the revised Ghent criteria and then subjected to molecular genetic analyses. FBN1 sequencing of the proband as well as available affected family members revealed the presence of a novel variant, c.7828G>C (p.Glu2610Gln), which was not present in any of the unaffected family members. In silico analyses demonstrated that the Glu2610 residue is part of the conserved DINE motif found at the beginning of each cbEGF domain of FBN1. The substitution of Glu2610 with Gln decreased fibrillin-1 production accordingly. Despite the fact that this variation appears to be primarily responsible for the etiology of MFS in the present family, our findings suggest that variable clinical expressions of the disease phenotype should be considered critically by the physicians.