Fig. 1. In vitro contracture test (IVCT) and genetic data of the family. ( A ) Pedigree of the family with a new putative heterozygous malignant hyperthermia (MH) mutation in the ryanodine receptor 1 (RYR1) gene. Four individuals of the second generation were tested with the IVCT; two of them were found to be MH susceptible (MHS) and had the W3985R variant ( striped symbols ), whereas the other two were diagnosed as normal (MHN) and did not carry the W3985R variant ( empty symbols ). The diagnosis in parentheses is based not on the IVCT result but on the occurrence of the W3985R variant. Individuals in the third generation were too young for the IVCT, and no blood samples were available. Gray symbols = no IVCT was performed. * Q11266E variant. ( B ) A base change in the codon for tryptophan 3985 (TGG → CGG) leads to the insertion of arginine at this position. Below is a linear representation of the primary sequence of the RYR1. Shaded boxes denote the so-called MH regions, domains of the protein that are thought to harbor most causative MH mutations. The new variant is at the beginning of the third MH domain but not related to any other known functional site of the protein. cDNA = complementary DNA.