Alternative titles; symbols
ORPHA: 423;
Cytogenetic location: 7q21-q22 Genomic coordinates (GRCh38) : 7:77,900,001-107,800,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 7q21-q22 | {Malignant hyperthermia susceptibility 3} | 154276 | Autosomal dominant | 2 |
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 (summary by Iles et al., 1994).
For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia susceptibility, see MHS1 (145600).
By linkage studies in 3 families, Sudbrak et al. (1993) excluded linkage either to chromosome 19 or 17q, thus suggesting the existence of a third locus for malignant hyperthermia susceptibility.
In MHS families linked to neither chromosome 17 nor chromosome 19, Iles et al. (1994) found linkage with no recombination to markers flanking the CACNA2D1 gene (114204) on chromosome 7. Since this gene encodes a subunit of the L-type voltage-dependent calcium channel that is intimately associated at the skeletal muscle triadic junctions with the ryanodine receptor (RYR1; 180901), it is possible that the mutation is located in this gene.
Exclusion Studies
In affected members of a family linked to the MHS3 locus by Iles et al. (1994), Schleithoff et al. (1999) did not identify any pathogenic mutations in the coding region of the CACNA2D1 gene.
Iles, D. E., Lehmann-Horn, F., Scherer, S. W., Tsui, L.-C., Olde Weghuis, D., Suijkerbuijk, R. F., Heytens, L., Mikala, G., Schwartz, A., Ellis, F. R., Stewart, A. D., Deufel, T., Wieringa, B. Localization of the gene encoding the alpha-2/delta-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. Hum. Molec. Genet. 3: 969-975, 1994. [PubMed: 7951247] [Full Text: https://doi.org/10.1093/hmg/3.6.969]
Schleithoff, L., Mehrke, G., Reutlinger, B., Lehmann-Horn, F. Genomic structure and functional expression of a human alpha-2/delta calcium channel subunit gene (CACNA2). Genomics 61: 201-209, 1999. [PubMed: 10534405] [Full Text: https://doi.org/10.1006/geno.1999.5941]
Sudbrak, R., Golla, A., Hogan, K., Powers, P., Gregg, R., Du Chesne, I., Lehmann-Horn, F., Deufel, T. Exclusion of malignant hyperthermia susceptibility (MHS) from a putative MHS2 locus on chromosome 17q and of the alpha-1, beta-1, and gamma subunits of the dihydropyridine receptor calcium channel as candidates for the molecular defect. Hum. Molec. Genet. 2: 857-862, 1993. [PubMed: 8395939] [Full Text: https://doi.org/10.1093/hmg/2.7.857]