Malignant Hyperthermia, Susceptibility To, 2

For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia, see MHS1 (145600).

In 3 unrelated families, Levitt et al. (1991) excluded linkage of the MHS phenotype to loci on 19q13.1, thus indicating genetic heterogeneity. Levitt et al. (1992) extended these studies to 16 MHS families. Four were found to be linked to chromosome 19; 5 were found to be closely linked to the anonymous marker NM23 (156490) on 17q11.2-q24 (maximum lod = 3.26 at theta = 0.0); and 2 families were clearly unlinked to either of these regions. In 5 additional families, there were insufficient data to determine their linkage status.

Olckers et al. (1992) provided evidence for linkage of MHS to the SCN4A gene (603967), which encodes the adult sodium channel alpha subunit, in 3 informative families (cumulative lod score of 2.1 at theta = 0.0). In a large family with autosomal dominant HYPP (170500) and MHS, Moslehi et al. (1998) found evidence for linkage of both disorders to the SCN4A locus on chromosome 17q (maximum lod for HYPP = 6.79 at theta = 0.0; lod for MHS = 1.76 at theta = 0.0).

In 3 families in which MHS did not show linkage to chromosome 19, Sudbrak et al. (1993) excluded linkage also to an 84-cM interval on 17q. At the same time, they excluded linkage to CACNL1A3, which is located on 1q, as well as to CACNLB1 (114207), CACNLG (114209), and SCN4A, which are located on 17q.