Factor 8 (F8) gene mutation profile of Turkish hemophilia A patients with inhibitors
| Autor: | Cetin Timur, Adalet Meral, Suat Caglayan, Kaan Kavakli, Uçar C, Yurdanur Kilinç, İnanç Değer Fidancı, Sayilan H, Elif Güler Kazanci |
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| Přispěvatelé: | Çukurova Üniversitesi, Uludağ Üniversitesi/Tıp Fakültesi/Hematoloji Anabilim dalı., Meral, Adalet Güneş |
| Rok vydání: | 2008 |
| Předmět: |
Male
Identification Turkey Intron Blood clotting factor 8 Gene mutation DNA splicing Treatment response Bioinformatics medicine.disease_cause Turkey (republic) Disease predisposition hemic and lymphatic diseases Missense mutation 3' Untranslated Regions Priority journal Mutation Point mutation Alloantibody Nonsense mutation Blood Coagulation Factor Inhibitors Coding Southern blotting Promoter region Hematology General Medicine Gene expression profiling Polymerase chain reaction Factor VIII gene Phenotype Tumor necrosis factor alpha Human congenital hereditary and neonatal diseases and abnormalities Chromosome inversion Clinical article DNA sequence Exon Biology Major histocompatibility complex Hemophilia A Article Inhibitors against Factor VIII Coagulopathy medicine Humans Disease severity Gene Factor Factor VIII Polymorphism Genetic Gene deletion 3' untranslated region medicine.disease Introns Single nucleotide polymorphism Alloimmunity Factor 8 gene mutation Immunology biology.protein |
| Zdroj: | Blood coagulationfibrinolysis : an international journal in haemostasis and thrombosis. 19(5) |
| ISSN: | 0957-5235 |
| Popis: | PubMedID: 18600086 Factor VIII (FVIII) replacement therapy is ineffective in hemophilia A patients who develop alloantibodies (inhibitors) against FVIII. The type of factor 8 (F8) gene mutation, genes in the major histocompatibility complex loci, and also polymorphisms in IL-10 and tumor necrosis factor-? are the major predisposing factors for inhibitor formation. The present study was initiated to reveal the F8 gene mutation profile of 30 severely affected high-responder patients with inhibitor levels of more than 5 Bethesda U (BU)/ml and four low-responder patients with inhibitors less than 5 BU/ml. Southern blot and PCR analysis were performed to detect intron 22 and intron 1 inversions, respectively. Point mutations were screened by DNA sequence analysis of all coding regions, intron/exon boundaries, promoter and 3' UTR regions of the F8 gene. The prevalent mutation was the intron 22 inversion among the high-responder patients followed by large deletions, small deletions, and nonsense mutations. Only one missense and one splicing error mutation was seen. Among the low-responder patients, three single nucleotide deletions and one intron 22 inversion were found. All mutation types detected were in agreement with the severe hemophilia A phenotype, most likely leading to a deficiency of and predisposition to the development of alloantibodies against FVIII. It is seen that Turkish hemophilia A patients with major molecular defects have a higher possibility of developing inhibitors. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. |
| Databáze: | OpenAIRE |
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