A case of discordance between genotype and phenotype in a malignant hyperthermia family.
Malignant hyperthermia (MH) is an inherited autosomal dominant pharmacogenetic disorder and is the major cause of anaesthesia-induced death. Malignant hyperthermia susceptibility is usually diagnosed by the in vitro contracture test (IVCT) performed on fresh muscle biopsies exposed to caffeine and halothane, respectively. Around 50% of affected families are linked to the ryanodine receptor (RYR1) gene. The human RYR1 gene maps to chromosome 19q13.1 and encodes a protein that associates as a homotetramer and acts as a calcium-release channel from the sarcoplasmic reticulum. To date, 17 mutations have been identified in the coding region of the RYR1 gene and appear to be associated to the MH-susceptible phenotype. Here we describe a rare case of discordance between genotype (characterised by the presence of the Arg614Cys mutation in the RYR1 gene) and MH-normal typed phenotype. Although the IVCT remains a very reliable procedure for the assessment of MH status, genetic data can provide in some cases an additional aid to clinical diagnosis.
Fortunato
G
G
Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II di Napoli, Italy.
Carsana
A
A
Tinto
N
N
Brancadoro
V
V
Canfora
G
G
Salvatore
F
F
D002110:Caffeine; D002888:Chromosomes, Human, Pair 19; D004198:Disease Susceptibility; D005190:Family; D005260:Female; D005838:Genotype; D006221:Halothane; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000235:genetics* / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D006221:Halothane