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Origin of Swedish hemophilia B mutations

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Author

Summary, in English

Background More than 1100 mutations that cause hemophilia B (HB) have been identified. At the same time, specific F9 mutations are present at high frequencies in certain populations, which raise questions about the origin of HB mutations. ObjectivesTo describe the mutation spectrum of all HB families in Sweden and investigate if mutations appearing in several families are due to independent recurrent mutations (RMs) or to a common mutation event (i.e. are identical by descent (IBD)). Patients/MethodsThe registered Swedish HB population consists of patients from 86 families. Mutations were identified by resequencing and identical haplotypes were defined using 74 markers and a control population of 285 individuals. The ages of IBD mutations were estimated using ESTIAGE. ResultsOut of 77 presumably unrelated patients with substitution mutations, 47 patients (61%) had mutations in common with other patients. Haplotyping of the 47 patients showed that 24 patients had IBD mutations (51%) with estimated ages of between two and 23 generations. A majority of these patients had mild disease. Eight of the 15 mutations observed in more than one family were C>T transitions in CpG sites and all eight were RMs. ConclusionsThe association of IBD mutations with a mild phenotype is similar to what has been previously observed in hemophilia A. Noteworthy features of the mutations that are common to more than one family are the equal proportions of patients with RM and IBD mutations and the correlation between the occurrence of RMs and C>T transitions at CpG sites.

Department/s

Publishing year

2013

Language

English

Pages

2001-2008

Publication/Series

Journal of Thrombosis and Haemostasis

Volume

11

Issue

11

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • factor IX
  • founder effect
  • haplotypes
  • hemophilia B
  • mutation

Status

Published

Research group

  • Paediatric Hematologic Research Group
  • Evolutionary Genetics
  • Paediatric Haematology Research Unit

ISBN/ISSN/Other

  • ISSN: 1538-7933