| 1. |
- Broman, M, et al.
(författare)
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Mutation screening of the RYR1-cDNA from peripheral B-lymphocytes in 15 Swedish malignant hyperthermia index cases.
- 2009
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 102:5, s. 642-649
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Islander, Gunilla, et al.
(författare)
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Male preponderance of patients testing positive for malignant hyperthermia susceptibility.
- 2007
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 51:5, s. 614-620
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Tidskriftsartikel (refereegranskat)abstract
- Malignant hyperthermia susceptibility is diagnosed using an in vitro contracture test (IVCT). In families in which the mutation is known, genetic tests are also available. The inheritance pattern is regarded as autosomal dominant, which predicts equal proportions of men and women affected. The aim of this study was to investigate whether there were sex differences in the diagnostic outcome of the 1407 patients tested for malignant hyperthermia in Sweden between 1985 and 2005. Methods: Information about sex, diagnosis, IVCT result and kinship was analysed. Comparisons were made between the two sexes. Probands and relatives were analysed separately in order to eliminate bias caused by the type of surgery performed in the two sexes. Results: Males, more than females, revealed a pathological outcome in IVCT. Amongst male relatives, the fraction of pathological outcome in IVCT was 0.70 [95% confidence interval (CI), 0.66-0.74]; the corresponding value for females was 0.40 (95% CI, 0.36-0.44). Conclusion: A significant difference was observed in the sex distribution of outcome of IVCT, with significantly more males revealing a pathological IVCT. This indicates the influence of one or several factors related to sex in the outcome of IVCT, for example different expression of calcium handling proteins in the sexes, a complex pattern of inheritance or unknown environmental factors.
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