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Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity

Ljung, Rolf LU ; Petrini, Pia; Tengborn, Lilian and Sjörin, Elsy LU (2001) In British Journal of Haematology 113(1). p.81-86
Abstract
The present series comprises all families (n = 77) with haemophilia B in Sweden and may be considered to be representative for the purposes of a population-based study of mutational heterogeneity. The 77 families (38 severe, 10 moderate, 29 mild) had 51 different mutations in total. Thirteen families had total, partial or small deletions, two had mutations in the promoter, eight families had splice site mutations, 14 had nonsense and the remaining 41 had missense mutations. Ten of the mutations, all C-->T or G-->A, recurred in 1--6 other families. Using haplotype analysis of seven polymorphisms in the factor IX (FIX) gene, we found that the 77 families carried 65 unique, independent mutations. Of the 48 families with severe or... (More)
The present series comprises all families (n = 77) with haemophilia B in Sweden and may be considered to be representative for the purposes of a population-based study of mutational heterogeneity. The 77 families (38 severe, 10 moderate, 29 mild) had 51 different mutations in total. Thirteen families had total, partial or small deletions, two had mutations in the promoter, eight families had splice site mutations, 14 had nonsense and the remaining 41 had missense mutations. Ten of the mutations, all C-->T or G-->A, recurred in 1--6 other families. Using haplotype analysis of seven polymorphisms in the factor IX (FIX) gene, we found that the 77 families carried 65 unique, independent mutations. Of the 48 families with severe or moderate haemophilia, 23 (48%) had a sporadic case of haemophilia compared with 31 families out of 78 (40%) in the whole series. Five of those 23 sporadic cases carried de novo mutations, 11 out of 23 of the mothers were proven carriers and, in the remaining seven families, it was not possible to determine carriership. Eleven of the 48 patients (23%) with severe haemophilia B developed inhibitors and all of them had deletions or nonsense mutations. Thus, 11 out of 37 (30%) patients with severe haemophilia B as a result of deletion/nonsense mutations developed inhibitors compared with 0 out of 11 patients with missense mutations. The ratio of male to female mutation rates was 5.3 and the overall mutation rate was 5.4 x 10(-6) per gamete per generation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
haemophilia B, factor IX, mutation, inhibitor, mutation frequency
in
British Journal of Haematology
volume
113
issue
1
pages
81 - 86
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • pmid:11328285
  • scopus:0035022048
ISSN
0007-1048
DOI
10.1046/j.1365-2141.2001.02759.x
language
English
LU publication?
yes
id
0830de0e-5843-44d4-9da1-6ba64c6aeb6b (old id 1122421)
date added to LUP
2008-07-04 10:58:14
date last changed
2018-06-07 12:21:16
@article{0830de0e-5843-44d4-9da1-6ba64c6aeb6b,
  abstract     = {The present series comprises all families (n = 77) with haemophilia B in Sweden and may be considered to be representative for the purposes of a population-based study of mutational heterogeneity. The 77 families (38 severe, 10 moderate, 29 mild) had 51 different mutations in total. Thirteen families had total, partial or small deletions, two had mutations in the promoter, eight families had splice site mutations, 14 had nonsense and the remaining 41 had missense mutations. Ten of the mutations, all C-->T or G-->A, recurred in 1--6 other families. Using haplotype analysis of seven polymorphisms in the factor IX (FIX) gene, we found that the 77 families carried 65 unique, independent mutations. Of the 48 families with severe or moderate haemophilia, 23 (48%) had a sporadic case of haemophilia compared with 31 families out of 78 (40%) in the whole series. Five of those 23 sporadic cases carried de novo mutations, 11 out of 23 of the mothers were proven carriers and, in the remaining seven families, it was not possible to determine carriership. Eleven of the 48 patients (23%) with severe haemophilia B developed inhibitors and all of them had deletions or nonsense mutations. Thus, 11 out of 37 (30%) patients with severe haemophilia B as a result of deletion/nonsense mutations developed inhibitors compared with 0 out of 11 patients with missense mutations. The ratio of male to female mutation rates was 5.3 and the overall mutation rate was 5.4 x 10(-6) per gamete per generation.},
  author       = {Ljung, Rolf and Petrini, Pia and Tengborn, Lilian and Sjörin, Elsy},
  issn         = {0007-1048},
  keyword      = {haemophilia B,factor IX,mutation,inhibitor,mutation frequency},
  language     = {eng},
  number       = {1},
  pages        = {81--86},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity},
  url          = {http://dx.doi.org/10.1046/j.1365-2141.2001.02759.x},
  volume       = {113},
  year         = {2001},
}