International Journal of Medical Laboratory

en ارزشیابی مولکولی و کلینیکی هفت بیمار ایرانی با کمبود شدید ارثی فاکتور V :کشف 4 موتاسیون جدید Molecular and Clinical Characterization of 7 Iranian Patients with Severe Congenital Factor V Deficiency: Identification of 4 Novel Mutations خون شناسی و بانک خون Hematology & Blood Banking پژوهشي Research It will be sent latter <div style="text-align: justify;">Background and Aims: Congenital factor V (FV) deficiency is a rare bleeding disorder with 1 in 1000000 persons in the general population. Individuals with FV activity <1% and very low FV antigen levels are characterized as severe FV deficient patients. Little data is available about the molecular basis of this bleeding disorder in Iran. Materials and Methods: We analyzed 7 unrelated Iranian FV deficient patients regarding clinical manifestation and genotype. The molecular dynamic simulation was carried out to analyze the effect of novel mutations on the FV structure.   Results: All cases had recurrence epistaxis, oral cavity bleeding, and hematoma were frequent in our patients. The molecular analysis led to the identification of three already reported mutations (IVS 19+3 A>T, 4014-4017 del TCAG and p.P419R) and four novel mutations (IVS9-1 G>C, Y478D, L1844P, I1556T) in the FV gene of our patients. According to the molecular modeling results, it seems that in the two mutations <a name="_Hlk76854275">Y478D</a> and <a name="_Hlk76854321">I1556T</a>, an increased number of H-bonds in mutant proteins compared to natural ones reduces the flexibility and increases the stability of the mutant proteins. The results also show that in L1844P and I1556T mutations, the total solvent accessible surface area (both hydrophilic and hydrophobic) significantly decreases compared to the natural variants.    Conclusion: Identifying the causative mutation in patients with FV deficiency helps to determine the molecular basis of this bleeding disorder and gain more insight into explaining the variable clinical manifestations of patients with FV deficiency.</div> کمبود فاکتور 5, موتاسیون, ارزشیابی کلینیکی , تجریک بنیادی سلولی Clinical manifestation, Factor V deficiency, Molecular dynamic, Mutation, Simulation 34 46 http://ijml.ssu.ac.ir/browse.php?a_code=A-10-463-1&slc_lang=en&sid=1 Sedigheh Satari صدیقه ستاری sattari.sedighe@gmail.com No Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran دانشگاه علوم پزشکی ایران Mahmood Shams محمود شمس mahmoodshams87@yahoo.com No Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska, Karolinska University Hospital Solna and Karolinska Institute, Stockholm, Sweden دانشگاه علوم پزشکی بابل Shadi Tabibian شادی طبیبیان sh.tabibian@gmail.com 0000-0002-9875-8391 No Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran دانشگاه علوم پزشکی ایران Farhad Zaker فرهاد ذاکر zaker.f@iums.ac.ir 0000-0001-7329-0297 No Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran دانشگاه علوم پزشکی ایران Mohammad Reza Rezvany محمد رضا رضوانی rezvani.mr@iums.ac.ir 0000-0003-0323-7671 Yes Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran دانشگاه علوم پزشکی ایران