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Origin of Swedish hemophilia B mutations

Hallden, C.; Mårtensson, Annika LU ; Nilsson, D.; Säll, Torbjörn LU ; Lind-Hallden, C.; Liden, A. C. and Ljung, Rolf LU (2013) In Journal of Thrombosis and Haemostasis 11(11). p.2001-2008
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
factor IX, founder effect, haplotypes, hemophilia B, mutation
in
Journal of Thrombosis and Haemostasis
volume
11
issue
11
pages
2001 - 2008
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000326764800008
  • scopus:84887560677
ISSN
1538-7933
DOI
10.1111/jth.12410
language
English
LU publication?
yes
id
ef72f4c9-fb8b-4ba2-ac46-d8b6ca7cefb0 (old id 4200995)
date added to LUP
2014-01-02 16:52:42
date last changed
2019-01-06 05:32:51
@article{ef72f4c9-fb8b-4ba2-ac46-d8b6ca7cefb0,
  abstract     = {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.},
  author       = {Hallden, C. and Mårtensson, Annika and Nilsson, D. and Säll, Torbjörn and Lind-Hallden, C. and Liden, A. C. and Ljung, Rolf},
  issn         = {1538-7933},
  keyword      = {factor IX,founder effect,haplotypes,hemophilia B,mutation},
  language     = {eng},
  number       = {11},
  pages        = {2001--2008},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Journal of Thrombosis and Haemostasis},
  title        = {Origin of Swedish hemophilia B mutations},
  url          = {http://dx.doi.org/10.1111/jth.12410},
  volume       = {11},
  year         = {2013},
}