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Mutation screening of the RYR1-cDNA from peripheral B-lymphocytes in 15 Swedish malignant hyperthermia index cases.

Broman, M; Gehrig, A; Islander, Gunilla LU ; Bodelsson, Mikael LU ; Ranklev Twetman, Eva LU ; Rüffert, H and Müller, C R (2009) In British Journal of Anaesthesia 102(5). p.642-649
Abstract
BACKGROUND: Malignant hyperthermia (MH), linked to the ryanodine receptor 1 gene (RYR1) on chromosome 19, is a potentially lethal pharmacogenetic disorder which may lead to a disturbance of intracellular calcium homeostasis when susceptible individuals are exposed to halogenated anaesthetics, suxamethonium, or both. Central core disease (CCD) is a rare dominantly inherited congenital myopathy allelic to MH-susceptibility. METHODS: In this study, 14 unrelated MH-susceptible probands and one CCD patient from Sweden were screened for mutations in the RYR1. Since the RYR1 is also expressed in B-lymphocytes, RYR1-cDNA was transcribed from total RNA extracted from white blood cells. RESULTS: We detected two known RYR1 mutations and two... (More)
BACKGROUND: Malignant hyperthermia (MH), linked to the ryanodine receptor 1 gene (RYR1) on chromosome 19, is a potentially lethal pharmacogenetic disorder which may lead to a disturbance of intracellular calcium homeostasis when susceptible individuals are exposed to halogenated anaesthetics, suxamethonium, or both. Central core disease (CCD) is a rare dominantly inherited congenital myopathy allelic to MH-susceptibility. METHODS: In this study, 14 unrelated MH-susceptible probands and one CCD patient from Sweden were screened for mutations in the RYR1. Since the RYR1 is also expressed in B-lymphocytes, RYR1-cDNA was transcribed from total RNA extracted from white blood cells. RESULTS: We detected two known RYR1 mutations and two previously described unclassified sequence variants. In addition, six novel sequence variants were detected. All mutations or sequence variants were verified on genomic DNA. Seven of the probands did not show any candidate mutation, although the total coding region of RYR1 was sequenced. Segregation data in in vitro contracture tested family members of three probands support a causative role of three of the novel sequence variants. CONCLUSIONS: Our study contributes to the genetic aetiology of MH in Sweden, but also raises questions about the involvement of genes other than RYR1 since nearly half of the probands did not show any sequence variants in the total coding region of the RYR1. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Anaesthesia
volume
102
issue
5
pages
642 - 649
publisher
Macmillan
external identifiers
  • wos:000265095300009
  • pmid:19346234
  • scopus:66149137664
ISSN
1471-6771
DOI
10.1093/bja/aep061
language
English
LU publication?
yes
id
0e902bd1-2d13-41df-8381-c9049b770d1f (old id 1392447)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19346234?dopt=Abstract
date added to LUP
2009-05-04 14:32:06
date last changed
2017-05-07 04:28:58
@article{0e902bd1-2d13-41df-8381-c9049b770d1f,
  abstract     = {BACKGROUND: Malignant hyperthermia (MH), linked to the ryanodine receptor 1 gene (RYR1) on chromosome 19, is a potentially lethal pharmacogenetic disorder which may lead to a disturbance of intracellular calcium homeostasis when susceptible individuals are exposed to halogenated anaesthetics, suxamethonium, or both. Central core disease (CCD) is a rare dominantly inherited congenital myopathy allelic to MH-susceptibility. METHODS: In this study, 14 unrelated MH-susceptible probands and one CCD patient from Sweden were screened for mutations in the RYR1. Since the RYR1 is also expressed in B-lymphocytes, RYR1-cDNA was transcribed from total RNA extracted from white blood cells. RESULTS: We detected two known RYR1 mutations and two previously described unclassified sequence variants. In addition, six novel sequence variants were detected. All mutations or sequence variants were verified on genomic DNA. Seven of the probands did not show any candidate mutation, although the total coding region of RYR1 was sequenced. Segregation data in in vitro contracture tested family members of three probands support a causative role of three of the novel sequence variants. CONCLUSIONS: Our study contributes to the genetic aetiology of MH in Sweden, but also raises questions about the involvement of genes other than RYR1 since nearly half of the probands did not show any sequence variants in the total coding region of the RYR1.},
  author       = {Broman, M and Gehrig, A and Islander, Gunilla and Bodelsson, Mikael and Ranklev Twetman, Eva and Rüffert, H and Müller, C R},
  issn         = {1471-6771},
  language     = {eng},
  number       = {5},
  pages        = {642--649},
  publisher    = {Macmillan},
  series       = {British Journal of Anaesthesia},
  title        = {Mutation screening of the RYR1-cDNA from peripheral B-lymphocytes in 15 Swedish malignant hyperthermia index cases.},
  url          = {http://dx.doi.org/10.1093/bja/aep061},
  volume       = {102},
  year         = {2009},
}