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Malignant hyperthermia and central core disease causative mutations in Swedish patients.

Broman, M; Islander, Gunilla LU ; Muller, C R and Ranklev Twetman, Eva LU (2007) In Acta Anaesthesiologica Scandinavica 51(Nov 1). p.50-53
Abstract
Background: Malignant hyperthermia (MH) susceptibility is a pharmacogenetic disorder of intracellular calcium homeostasis. In susceptible individuals, halogenated anaesthetics and/or suxamethonium may trigger an MH reaction. The diagnosis of MH susceptibility is made by an in vitro contracture test of biopsied muscle strips. Methods: In 27 MH susceptible (MHS) probands and four MH negative (MHN) probands, exons 17, 39, 40, 45 and 46 of the RYR1 gene were screened for MH causative mutations. In addition, in three patients with established central core disease (CCD), exons 17, 39, 40, 45 and 46 and exons 95, 100, 101 and 102 were screened for MH and CCD causative mutations. All screenings were performed by direct sequencing of the entire... (More)
Background: Malignant hyperthermia (MH) susceptibility is a pharmacogenetic disorder of intracellular calcium homeostasis. In susceptible individuals, halogenated anaesthetics and/or suxamethonium may trigger an MH reaction. The diagnosis of MH susceptibility is made by an in vitro contracture test of biopsied muscle strips. Methods: In 27 MH susceptible (MHS) probands and four MH negative (MHN) probands, exons 17, 39, 40, 45 and 46 of the RYR1 gene were screened for MH causative mutations. In addition, in three patients with established central core disease (CCD), exons 17, 39, 40, 45 and 46 and exons 95, 100, 101 and 102 were screened for MH and CCD causative mutations. All screenings were performed by direct sequencing of the entire exons. Results: MH causative mutations were found in five of the 27 MHS probands (19%). CCD causative mutations were found in two of three CCD patients in the C-terminal exons. None of the CCD patients showed a mutation in N-terminal exon 17 or in the central exons. Conclusions: In a Swedish population, screening of N-terminal exon 17 and the central exons for MH causative mutations in the RYR1 gene covers 19% of families. Thus, other mutations must also be responsible for MH susceptibility in Sweden. Although the number of CCD patients in this study was small, screening of the C-terminal exons for CCD causative mutations seems to be a promising tool in the process of making a diagnosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
malignant hyperthermia, central core disease, Swedish probands, genetic screening
in
Acta Anaesthesiologica Scandinavica
volume
51
issue
Nov 1
pages
50 - 53
publisher
Wiley-Blackwell
external identifiers
  • wos:000242902400008
  • scopus:33845709024
ISSN
0001-5172
DOI
10.1111/j.1399-6576.2006.01165.x
language
English
LU publication?
yes
id
20c0fa51-36b0-4647-b286-b05dfb2fbee3 (old id 163469)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17081152&dopt=Abstract
date added to LUP
2007-06-27 13:49:39
date last changed
2017-01-01 04:42:00
@article{20c0fa51-36b0-4647-b286-b05dfb2fbee3,
  abstract     = {Background: Malignant hyperthermia (MH) susceptibility is a pharmacogenetic disorder of intracellular calcium homeostasis. In susceptible individuals, halogenated anaesthetics and/or suxamethonium may trigger an MH reaction. The diagnosis of MH susceptibility is made by an in vitro contracture test of biopsied muscle strips. Methods: In 27 MH susceptible (MHS) probands and four MH negative (MHN) probands, exons 17, 39, 40, 45 and 46 of the RYR1 gene were screened for MH causative mutations. In addition, in three patients with established central core disease (CCD), exons 17, 39, 40, 45 and 46 and exons 95, 100, 101 and 102 were screened for MH and CCD causative mutations. All screenings were performed by direct sequencing of the entire exons. Results: MH causative mutations were found in five of the 27 MHS probands (19%). CCD causative mutations were found in two of three CCD patients in the C-terminal exons. None of the CCD patients showed a mutation in N-terminal exon 17 or in the central exons. Conclusions: In a Swedish population, screening of N-terminal exon 17 and the central exons for MH causative mutations in the RYR1 gene covers 19% of families. Thus, other mutations must also be responsible for MH susceptibility in Sweden. Although the number of CCD patients in this study was small, screening of the C-terminal exons for CCD causative mutations seems to be a promising tool in the process of making a diagnosis.},
  author       = {Broman, M and Islander, Gunilla and Muller, C R and Ranklev Twetman, Eva},
  issn         = {0001-5172},
  keyword      = {malignant hyperthermia,central core disease,Swedish probands,genetic screening},
  language     = {eng},
  number       = {Nov 1},
  pages        = {50--53},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Anaesthesiologica Scandinavica},
  title        = {Malignant hyperthermia and central core disease causative mutations in Swedish patients.},
  url          = {http://dx.doi.org/10.1111/j.1399-6576.2006.01165.x},
  volume       = {51},
  year         = {2007},
}