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Large deletions of the PROS1 gene in a large fraction of mutationnegative patients with protein S deficiency

Johansson, Anna LU ; Hillarp, Andreas LU ; Säll, Torbjörn LU ; Zöller, Bengt LU ; Dahlbäck, Björn LU and Halldén, Christer LU (2005) In Thrombosis and Haemostasis 94(5). p.951-957
Abstract
Protein S deficiency is an autosomal dominant disorder that results from mutations in the PROS I gene. Conventional mutation detection techniques fail to detect a pathogenic PROSI mutation in approximately 50% of cases. The present study investigates whether large deletions of PROS I are found in families where mutations in the PROS I gene have not been found despite sequencing. For this purpose, a dense set of SNP and microsatellite markers were used in segregation analysis to identify deletions. Large deletions were identified by this technique in three out of eight investigated families (38%). The deletions en-compassed at least 35 kb, 437 kb and 449 kb respectively. The deletions were confirmed by quantitative PCR. Haplotype analysis... (More)
Protein S deficiency is an autosomal dominant disorder that results from mutations in the PROS I gene. Conventional mutation detection techniques fail to detect a pathogenic PROSI mutation in approximately 50% of cases. The present study investigates whether large deletions of PROS I are found in families where mutations in the PROS I gene have not been found despite sequencing. For this purpose, a dense set of SNP and microsatellite markers were used in segregation analysis to identify deletions. Large deletions were identified by this technique in three out of eight investigated families (38%). The deletions en-compassed at least 35 kb, 437 kb and 449 kb respectively. The deletions were confirmed by quantitative PCR. Haplotype analysis showed that the three large deletions and the five other disease haplotypes were all different. All of the eight disease haplotypes co-segregated with protein S deficiency, but each of the five non-deletion haplotypes were present also in normal individuals. In conclusion: Large deletions of PROS I are relatively common in protein S deficiency patients and screening for large deletions in PROS I mutation-negative individuals are therefore warranted. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
protein S deficiency, deletion, mutation, PROS I
in
Thrombosis and Haemostasis
volume
94
issue
5
pages
951 - 957
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • wos:000233377900009
  • pmid:16363235
  • scopus:27844561552
ISSN
0340-6245
DOI
10.1160/TH05-06-0392
language
English
LU publication?
yes
id
fee695e1-7e86-4f85-ad67-867f9568af0e (old id 212447)
date added to LUP
2007-08-16 14:02:45
date last changed
2017-01-01 07:19:52
@article{fee695e1-7e86-4f85-ad67-867f9568af0e,
  abstract     = {Protein S deficiency is an autosomal dominant disorder that results from mutations in the PROS I gene. Conventional mutation detection techniques fail to detect a pathogenic PROSI mutation in approximately 50% of cases. The present study investigates whether large deletions of PROS I are found in families where mutations in the PROS I gene have not been found despite sequencing. For this purpose, a dense set of SNP and microsatellite markers were used in segregation analysis to identify deletions. Large deletions were identified by this technique in three out of eight investigated families (38%). The deletions en-compassed at least 35 kb, 437 kb and 449 kb respectively. The deletions were confirmed by quantitative PCR. Haplotype analysis showed that the three large deletions and the five other disease haplotypes were all different. All of the eight disease haplotypes co-segregated with protein S deficiency, but each of the five non-deletion haplotypes were present also in normal individuals. In conclusion: Large deletions of PROS I are relatively common in protein S deficiency patients and screening for large deletions in PROS I mutation-negative individuals are therefore warranted.},
  author       = {Johansson, Anna and Hillarp, Andreas and Säll, Torbjörn and Zöller, Bengt and Dahlbäck, Björn and Halldén, Christer},
  issn         = {0340-6245},
  keyword      = {protein S deficiency,deletion,mutation,PROS I},
  language     = {eng},
  number       = {5},
  pages        = {951--957},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {Large deletions of the PROS1 gene in a large fraction of mutationnegative patients with protein S deficiency},
  url          = {http://dx.doi.org/10.1160/TH05-06-0392},
  volume       = {94},
  year         = {2005},
}