Thirteen novel mutations in the factor VIII gene in the Nijmegen haemophilia A patient population
| Autor: | Bert Verbruggen, Jorien Boekhorst, Jean Maurice Lavergne, Jean-Marc Costa, Irena Novakova, Paul P. T. Brons, S.C.M. Schoormans, Marian G.J. van Kraaij, Waander L. van Heerde |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Heterozygote Adolescent Genotype Bioinformatics DNA Mutational Analysis Haemophilia A Population Vascular medicine and diabetes [UMCN 2.2] Hemophilia A medicine.disease_cause Risk Assessment Invasive mycoses and compromised host [N4i 2] Cohort Studies Exon Humans Medicine Missense mutation Child education Aged Aged 80 and over Genetics Mutation education.field_of_study Factor VIII Cardiovascular diseases [NCEBP 14] Blood Coagulation Factor Inhibitors business.industry Haplotype Infant Immunotherapy gene therapy and transplantation [UMCN 1.4] Exons Hematology Middle Aged medicine.disease Virology Phenotype Protein Structure Tertiary Haplotypes Child Preschool Female business |
| Zdroj: | British Journal of Haematology, 131, 109-17 British Journal of Haematology, 131, 1, pp. 109-17 |
| ISSN: | 0007-1048 |
| Popis: | Contains fulltext : 33158.pdf (Publisher’s version ) (Closed access) The development of neutralising antibodies to factor VIII (FVIII) is a major complication of haemophilia A (HA) therapy. We aimed to construct an individual risk profile for the development of inhibitors in HA and started by screening for the causative mutation in our HA patient population. A total of 109 patients and 28 carriers were screened. The analysis revealed 38 different mutations in the FVIII gene, of which 13 have not been described on the Haemophilia A Mutation, Search, Test and Resource Site (HAMSTeRS). Twenty-five mutations have been reported previously and all except two had a similar phenotype to what has been described. Three novel mutations were associated with severe HA: one non-missense mutation, a small insertion in the A2 domain, and two missense mutations, a H256R mutation in the A1 domain and a L2025P substitution in the C1 domain. One novel mutation, Y156C, was associated with moderate HA. Nine novel mutations caused mild HA. The P130R, D167E and V278M mutations are located in the A1 domain. R439C, Y511H, A544G and Q645H in the A2 domain, L1758F in the A3 domain and a S2157R mutation in the C1 domain. In conclusion, the genotypic profile of our HA population was not different from others described and is suitable to study inhibitor formation. |
| Databáze: | OpenAIRE |
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