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Small and large PROS1 deletions but no other types of rearrangements detected in patents with protein S deficiency

Lind-Hallden, Christina; Dahlen, Anna; Hillarp, Andreas LU ; Zöller, Bengt LU ; Dahlbäck, Björn LU and Hallden, Christer (2012) In Thrombosis and Haemostasis 108(1). p.94-100
Abstract
Protein S deficiency is a dominantly inherited disorder that results from mutations in the PROS] gene. Previous sequencing of the gene failed to detect mutations in eight out of 18 investigated Swedish families, whereas segregation analyses detected large deletions in three out of the eight families. The present study investigates more thoroughly for the presence of deletions but also for other types of rearrangements. FISH analysis confirmed the existence of the three previously identified large deletions, but failed to identify any other type of rearrangement among the eight analysed families. MLPA analysis of the PROS1 gene revealed two smaller deletions covering two and four exons, respectively. Thus, deletions could be found in five... (More)
Protein S deficiency is a dominantly inherited disorder that results from mutations in the PROS] gene. Previous sequencing of the gene failed to detect mutations in eight out of 18 investigated Swedish families, whereas segregation analyses detected large deletions in three out of the eight families. The present study investigates more thoroughly for the presence of deletions but also for other types of rearrangements. FISH analysis confirmed the existence of the three previously identified large deletions, but failed to identify any other type of rearrangement among the eight analysed families. MLPA analysis of the PROS1 gene revealed two smaller deletions covering two and four exons, respectively. Thus, deletions could be found in five out of eight families where no point mutations could be found despite sequencing of the gene. Twelve additional, not previously analysed, families were subsequently analysed using MLPA. The analysis identified two smaller deletions (3 and 4 exons). Including all PS-deficient families, i.e. also the 10 families where sequencing found a causative point mutation, deletions were identified in seven out of 30 PS-deficient families. A strategy of sequencing followed by MLPA analysis in mutation-negative families identified the causative mutation in 15 out of 18 of Swedish PS-deficient families. Most deletions were different as determined by their sizes, locations and flanking haplotypes. FISH (8 families) and MLPA analysis (20 families) failed to identify other types of rearrangements. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Protein C/S pathway, molecular biology methods, familial thrombosis, venous thrombosis, thrombophilia
in
Thrombosis and Haemostasis
volume
108
issue
1
pages
94 - 100
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • wos:000306538400014
  • scopus:84863645771
ISSN
0340-6245
DOI
10.1160/TH12-01-0040
language
English
LU publication?
yes
id
58bad3ec-7a2a-47b7-bc8c-23aa7eace600 (old id 2979365)
date added to LUP
2012-09-03 07:16:13
date last changed
2017-01-01 05:53:05
@article{58bad3ec-7a2a-47b7-bc8c-23aa7eace600,
  abstract     = {Protein S deficiency is a dominantly inherited disorder that results from mutations in the PROS] gene. Previous sequencing of the gene failed to detect mutations in eight out of 18 investigated Swedish families, whereas segregation analyses detected large deletions in three out of the eight families. The present study investigates more thoroughly for the presence of deletions but also for other types of rearrangements. FISH analysis confirmed the existence of the three previously identified large deletions, but failed to identify any other type of rearrangement among the eight analysed families. MLPA analysis of the PROS1 gene revealed two smaller deletions covering two and four exons, respectively. Thus, deletions could be found in five out of eight families where no point mutations could be found despite sequencing of the gene. Twelve additional, not previously analysed, families were subsequently analysed using MLPA. The analysis identified two smaller deletions (3 and 4 exons). Including all PS-deficient families, i.e. also the 10 families where sequencing found a causative point mutation, deletions were identified in seven out of 30 PS-deficient families. A strategy of sequencing followed by MLPA analysis in mutation-negative families identified the causative mutation in 15 out of 18 of Swedish PS-deficient families. Most deletions were different as determined by their sizes, locations and flanking haplotypes. FISH (8 families) and MLPA analysis (20 families) failed to identify other types of rearrangements.},
  author       = {Lind-Hallden, Christina and Dahlen, Anna and Hillarp, Andreas and Zöller, Bengt and Dahlbäck, Björn and Hallden, Christer},
  issn         = {0340-6245},
  keyword      = {Protein C/S pathway,molecular biology methods,familial thrombosis,venous thrombosis,thrombophilia},
  language     = {eng},
  number       = {1},
  pages        = {94--100},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Small and large PROS1 deletions but no other types of rearrangements detected in patents with protein S deficiency},
  url          = {http://dx.doi.org/10.1160/TH12-01-0040},
  volume       = {108},
  year         = {2012},
}