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Origin of Swedish hemophilia A mutations

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Author

Summary, in English

Background: Hemophilia A (HA) has a high level of variation within the disease class, with more than 1000 mutations being listed in the HAMSTeRS database. At the same time a number of F8 mutations are present in specific populations at high frequencies. Objectives: The simultaneous presence of large numbers of rare mutations and a small number of high-frequency mutations raises questions about the origins of HA mutations. The present study was aimed at describing the origins of HA mutations in the complete Swedish population. The primary issue was to determine what proportion of identical mutations are identical by descent (IBD) and what proportion are attributable to recurrent mutation events. The age of IBD mutations was also determined. Patients/Methods: In Sweden, the care of HA is centralized, and the Swedish HA population consists of 750 patients from > 300 families (35% severe, 15% moderate, and 50% mild). Identical haplotypes were defined by single-nucleotide polymorphism and microsatellite haplotyping, and the ages of the mutations were estimated with estiage. Results: Among 212 presumably unrelated patients with substitution mutations, 97 (46%) had mutations in common with other patients. Haplotyping of the 97 patients showed that 47 had IBD mutations (22%) with estimated ages of between two and 35 generations. The frequency of mild disease increased with an increasing number of patients sharing the mutations. Conclusions: A majority of the IBD mutations are mild and have age estimates of a few hundred years, but some could date back to the Middle Ages.

Department/s

Publishing year

2012

Language

English

Pages

2503-2511

Publication/Series

Journal of Thrombosis and Haemostasis

Volume

10

Issue

12

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Hematology
  • Pediatrics

Keywords

  • founder
  • haplotype
  • hemophilia A
  • identical by descent
  • recurrent
  • mutation

Status

Published

Research group

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

ISBN/ISSN/Other

  • ISSN: 1538-7933