RT Journal Article SR Electronic T1 Genetic heterogeneity and HOMOG analysis in British malignant hyperthermia families. JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 196 OP 201 DO 10.1136/jmg.35.3.196 VO 35 IS 3 A1 R Robinson A1 J L Curran A1 W J Hall A1 P J Halsall A1 P M Hopkins A1 A F Markham A1 A D Stewart A1 S P West A1 F R Ellis YR 1998 UL http://jmg.bmj.com/content/35/3/196.abstract AB Malignant hyperthermia (MH) is an autosomal dominant genetic condition that presents in susceptible people undergoing general anaesthesia. The clinical disorder is a major cause of anaesthetic morbidity and mortality. The UK Malignant Hyperthermia Group has performed genetic linkage analysis on 20 large, well defined malignant hyperthermia families, using hypervariable markers on chromosome 19q13.1, including the candidate MH gene RYR1, the gene coding for the skeletal muscle ryanodine receptor protein. The results were analysed using LINKAGE to perform two point and multipoint lod scores, then HOMOG to calculate levels of heterogeneity. The results clearly showed genetic heterogeneity between MH families; nine of the families gave results entirely consistent with linkage to the region around RYR1 while the same region was clearly excluded in three families. In the remaining eight MHS families there were single recombinant events between RYR1 and MH susceptibility. HOMOG analysis was of little added benefit in determining the likelihood of linkage to RYR1 in these families. This confirmation of the presence of heterogeneity in the UK MH population, along with the possibility of the presence of two MH genes in some pedigrees, indicates that it would be premature and potentially dangerous to offer diagnosis of MH by DNA based methods at this time.