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Investigation of disease-associated factors in haemophilia A patients without detectable mutations.

Halldén, Christer LU ; Knobe, Karin LU ; Sjörin, Elsy LU ; Nilsson, David LU and Ljung, Rolf LU (2012) In Haemophilia 18(3). p.132-137
Abstract
Summary. To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive... (More)
Summary. To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive patients carrying the same haplotypes as the mutation-negative patients show a multitude of different mutations, emphasizing the lack of associations at the haplotype level. VWF mutation screening and factor V measurements ruled out type 2N VWD and combined factor V and VIII deficiency respectively. To further investigate a possible role for FVIII interacting factors the haplotypes/diplotypes of F2, F9, F10 and VWF were compared. The nine patients had no specific haplotype/diplotype combination in common that can explain disease. Duplications and faulty transcription contribute to the mutational spectrum of haemophilia A patients where conventional mutation screening fail to identify mutations. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Haemophilia
volume
18
issue
3
pages
132 - 137
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000303194200023
  • pmid:22221887
  • scopus:84860348909
ISSN
1351-8216
DOI
10.1111/j.1365-2516.2011.02737.x
language
English
LU publication?
yes
id
7f39583c-75f6-4a69-a6f3-115898d59df8 (old id 2336654)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22221887?dopt=Abstract
date added to LUP
2012-02-01 19:47:51
date last changed
2017-01-01 07:36:31
@article{7f39583c-75f6-4a69-a6f3-115898d59df8,
  abstract     = {Summary. To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive patients carrying the same haplotypes as the mutation-negative patients show a multitude of different mutations, emphasizing the lack of associations at the haplotype level. VWF mutation screening and factor V measurements ruled out type 2N VWD and combined factor V and VIII deficiency respectively. To further investigate a possible role for FVIII interacting factors the haplotypes/diplotypes of F2, F9, F10 and VWF were compared. The nine patients had no specific haplotype/diplotype combination in common that can explain disease. Duplications and faulty transcription contribute to the mutational spectrum of haemophilia A patients where conventional mutation screening fail to identify mutations.},
  author       = {Halldén, Christer and Knobe, Karin and Sjörin, Elsy and Nilsson, David and Ljung, Rolf},
  issn         = {1351-8216},
  language     = {eng},
  number       = {3},
  pages        = {132--137},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Haemophilia},
  title        = {Investigation of disease-associated factors in haemophilia A patients without detectable mutations.},
  url          = {http://dx.doi.org/10.1111/j.1365-2516.2011.02737.x},
  volume       = {18},
  year         = {2012},
}