Localization of the gene encoding the α2/δ-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families

D. E. Iles, F. Lehmann-Horn, S. W. Scherer, L. C. Tsui, D. Olde Weghuis, R. F. Suljkerbuijk, L. Heytens, G. Mikala, A. Schwartz, F. R. Ellis, A. D. Stewart, T. Deufel, B. Wieringa

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Malignant hyperthermia susceptibility (MHS) is an autosomal dominant disorder of skeletal muscle which manifests as a potentially fatal hypermetabolic crisis triggered by commonly used anaesthetic agents. The demonstration of genetic heterogeneity in MHS prompted the investigation of the roles played by calcium regulatory proteins other than the ryanodine receptor (RYR1), which is known to be linked to MHS in fewer than half of the European MHS families studied to date. Previously, we have excluded the genes encoding the skeletal muscle L-type voltage-dependent calcium channel α1-, β1,- and γ-subunits as candidates for MHS. In this report, we describe the cloning and partial DNA sequence analysis of the gene encoding the α2/δ-subunits, CACNL2A, and its localization on the proximal long arm of chromosome 7q. A new dinucleotide repeat marker close to CACNL2A was identified at the D7S849 locus and tested for linkage in six MHS families. D7S849 and flanking genetic markers were found to co-segregate with the MHS locus through 11 meioses in one, three-generation family. These results suggest that mutations in or near CACNL2A may be involved in some forms of this heterogeneous disorder.

Original languageEnglish
Pages (from-to)969-975
Number of pages7
JournalHuman Molecular Genetics
Volume3
Issue number6
Publication statusPublished - Jun 1994

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Hyperthermia
Malignant Hyperthermia
L-Type Calcium Channels
Gene encoding
Segregation
Chromosomes
Calcium
Susceptibility
Chromosome
Muscle
Encoding
Voltage
Gene
Anesthetics
Dependent
Cloning
DNA sequences
Electric potential
Genes
Demonstrations

ASJC Scopus subject areas

  • Genetics
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Molecular Biology
  • Genetics(clinical)

Cite this

Localization of the gene encoding the α2/δ-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. / Iles, D. E.; Lehmann-Horn, F.; Scherer, S. W.; Tsui, L. C.; Olde Weghuis, D.; Suljkerbuijk, R. F.; Heytens, L.; Mikala, G.; Schwartz, A.; Ellis, F. R.; Stewart, A. D.; Deufel, T.; Wieringa, B.

In: Human Molecular Genetics, Vol. 3, No. 6, 06.1994, p. 969-975.

Research output: Contribution to journalArticle

Iles, DE, Lehmann-Horn, F, Scherer, SW, Tsui, LC, Olde Weghuis, D, Suljkerbuijk, RF, Heytens, L, Mikala, G, Schwartz, A, Ellis, FR, Stewart, AD, Deufel, T & Wieringa, B 1994, 'Localization of the gene encoding the α2/δ-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families', Human Molecular Genetics, vol. 3, no. 6, pp. 969-975.
Iles, D. E. ; Lehmann-Horn, F. ; Scherer, S. W. ; Tsui, L. C. ; Olde Weghuis, D. ; Suljkerbuijk, R. F. ; Heytens, L. ; Mikala, G. ; Schwartz, A. ; Ellis, F. R. ; Stewart, A. D. ; Deufel, T. ; Wieringa, B. / Localization of the gene encoding the α2/δ-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. In: Human Molecular Genetics. 1994 ; Vol. 3, No. 6. pp. 969-975.
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