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Origin of Swedish hemophilia A mutations

Halldén, C.; Nilsson, D.; Säll, Torbjörn LU ; Lind-Hallden, C.; Liden, A. C. and Ljung, Rolf LU (2012) In Journal of Thrombosis and Haemostasis 10(12). p.2503-2511
Abstract
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.... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
founder, haplotype, hemophilia A, identical by descent, recurrent, mutation
in
Journal of Thrombosis and Haemostasis
volume
10
issue
12
pages
2503 - 2511
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000312539600011
  • scopus:84871086406
ISSN
1538-7933
DOI
10.1111/jth.12010
language
English
LU publication?
yes
id
a8369110-25e7-4346-8da9-b6edca713c93 (old id 3366249)
date added to LUP
2013-01-23 12:44:57
date last changed
2017-01-01 03:31:52
@article{a8369110-25e7-4346-8da9-b6edca713c93,
  abstract     = {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.},
  author       = {Halldén, C. and Nilsson, D. and Säll, Torbjörn and Lind-Hallden, C. and Liden, A. C. and Ljung, Rolf},
  issn         = {1538-7933},
  keyword      = {founder,haplotype,hemophilia A,identical by descent,recurrent,mutation},
  language     = {eng},
  number       = {12},
  pages        = {2503--2511},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {Origin of Swedish hemophilia A mutations},
  url          = {http://dx.doi.org/10.1111/jth.12010},
  volume       = {10},
  year         = {2012},
}