Origin of swedish haemophilia a mutations.
Publikation/Tidskrift/Serie: Journal of thrombosis and haemostasis : JTH
Background: Haemophilia A (HA) has a high level of variation within the disease class with more than 1000 mutations 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 aims to describe the origins of HA mutations in the complete Swedish population. The primary issue is to determine what proportion of identical mutations is identical by descent (IBD) and what proportion is due to recurrent mutation events. The age of IBD mutations will also be determined. Patients/Methods: In Sweden the care of HA is centralized and the Swedish HA population consists of approximately 750 patients from more than 300 families (35% severe, 15% moderate and 50% mild form). Identical haplotypes were defined using SNP and microsatellite haplotyping and the ages of the mutations estimated using Estiage. Results: Out of 212 presumably unrelated patients with substitution mutations, 97 patients. (46%) had mutations in common with other patients. Haplotyping of the 97 patients showed that 47 patients had IBD mutations (22%) with estimated ages of between 2 and 35 generations. The frequency of mild disease increases with 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. © 2012 International Society on Thrombosis and Haemostasis.
- Medicine and Health Sciences
- ISSN: 1538-7836