Browsing by Author "Ustek, Duran"

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A Homozygous Nonsense Thyroid Peroxidase Mutation (R540x) Consistently Causes Congenital Hypothyroidism in Two Siblings Born To a Consanguineous Family
(Galenos Yayincilik, 2015) Cangul, Hakan; Dogan, Murat; Ustek, Duran
Objective: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, and mutations in the thyroid peroxidase (TPO) gene have been reported to cause the disease. Our aim in this study was to determine the genetic basis of CH in two affected children coming from a consanguineous family. Methods: First, we investigated the potential genetic linkage of the family to any known CH locus using microsatellite markers and then screened for mutations in the linked gene by Sanger sequencing. By using next-generation sequencing, we also checked if any other mutation was present in the remaining 10 causative CH genes. Results: The family showed potential linkage to the TPO gene, and we detected a homozygous nonsense mutation (R540X) in both cases. The two patients had total iodide organification defect (TIOD). Both the microsatellite marker haplotypes and the mutation segregated with the disease status in the family, i.e. all healthy subjects were either heterozygous carriers or homozygous wild-type, confirming the pathogenic nature of the mutation. Neither was the mutation present in any of the 400 control chromosomes nor were there any other mutations in the remaining causative CH genes. Conclusion: This study proves the pathogenicity of R540X mutation and demonstrates the strong genotype/phenotype correlation associated with this mutation. It also highlights the power of working with familial cases in revealing the molecular basis of CH and in establishing accurate genotype/phenotype relationships associated with disease causing mutations.
Topical Single-Dose Vascular Endothelial Growth Factor Has No Effect on Soft Tissue Healing
(Medknow Publications & Media Pvt Ltd, 2014) Bolukbasi, Nilufer; Balcioglu, Huseyin Avni; Ozkan, Birkan T.; Tekkesin, Merva Soluk; Ustek, Duran
Background: Vascular endothelial growth factor (VEGF) production in dermal wounds has been evaluated for evidence that it plays a probable role in wound healing. Events such as increased vascular permeability and concentration of inflammatory cells on the site of injury, produced by VEGF, were linked to tissue repair. Aim: The present study aimed to evaluate the effects of single-dose topical administration of VEGF on wound healing. Materials and Methods: A total of 30 male Wistar albino rats weighing 250-280 g were used in this study. In addition, 2-cm-long skin incisions were created over bilaterally exposed skin of the tibia region in each rat. VEGF plasmid 2 mg was administered locally into the right side wound bed of each animal. No other procedure besides skin closure was administered on the left side. To determine histologic assessments, skin samples were obtained from six anesthetized rats at each interval (4, 8, 12, 16 and 30 days) through excisional biopsy. The tissues were fixed in 10% neutral-buffered formalin for 1 week and then embedded in paraffin wax. Transverse sections of the embedded tissue 5-7 mm thick were stained with hematoxylin and eosin (H and E). Results: There was no significant difference regarding necrosis, epithelialization, inflammation, fibroblast activity, ulcerative formation, or hemorrhage between experimental and control groups. No statistically significant difference was found between the groups regarding granulation tissue formation and epidermal thickness. Conclusion: The administration method and dosage of VEGF is a major factor in terms of its effectiveness. The results of the present study did not evaluate the effectiveness of single-dose 2 mg topical administration of VEGF; however, various doses of VEGF plasmid should be tested in future studies in order to provide beneficial effects from topical administration of VEGF.