CACNA1S mutations

In addition to the RYR1 mutations listed below there are two mutations in the dihydropyridine recepter (Gen: CACNA1S) which are accepted as diagnostic mutations by the EMHG.

  • p.Arg1086His  c.3257G>A
  • p.Arg174Trp   c.520C>T

References:

Weiss RG, O’Connell KM, Flucher BE, Allen PD, Grabner M, Dirksen RT.  Functional analysis of the R1086H malignant hyperthermia mutation in the DHPR reveals an unexpected influence of the III-IV loop on skeletal muscle EC coupling. Am J Physiol Cell Physiol 2004; 287: C1094-102

Eltit JM, Bannister RA, Moua O, Altamirano F, Hopkins PM, Pessah IN, Molinski TF, Lopez JR, Beam KG, Allen PD: Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca2+ channel and the type 1 ryanodine receptor. Proc Natl Acad Sci U S A 2012; 109: 7923-8

Guidelines for genetic testing in MH

The EMHG has published guidelines about the criteria to classify mutations as diagnostic (causative). These guidelines can be downloaded

Presence of a diagnostic (causative) mutation allows for the diagnosis of MH susceptibility. Absence of such mutation(s) do not allow for any diagnosis. MH can only be excluded by contracture testing. See EMHG guidelines on genetic testing for MH susceptibility.