Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia.
Hypokalemic periodic paralysis (HypoPP) and malignant hyperthermia (MH) are autosomal-dominant genetically heterogeneous ion channelopathies. MH has been described in patients with HypoPP, suggesting a potential link between these disorders. However, a common genetic determinant has not been described. With the aim of corroborating this association, four candidate genes were screened in two independent HypoPP patients, one of whom was also diagnosed as MH-susceptible and the other as MH-normal by the in vitro contracture test (IVCT). An A>G change at nucleotide 7025 was detected in the RYR1 gene in the HypoPP/MH-susceptible patient. Detection of the same mutation in three independent MH families suggested that 7025A>G represents a novel MH-susceptibility allele and that MH and HypoPP occurred independently in the case presented. Conclusive evidence in support of the hypothesis that MH and HypoPP are allelic was therefore not obtained.
Marchant
Clare L
CL
Malignant Hyperthermia Investigation Unit, Academic Unit of Anesthesia, Level 8 Clinical Sciences Building, St. James University Hospital, Beckett Street, Leeds LS9 7TF, UK.
Ellis
F Richard
FR
Halsall
P Jane
PJ
Hopkins
Philip M
PM
Robinson
Rachel L
RL
D000293:Adolescent; D000328:Adult; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type; D004252:DNA Mutational Analysis; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000235:genetics*; D008297:Male; D008305:Malignant Hyperthermia / Q000235:genetics*; D062553:NAV1.4 Voltage-Gated Sodium Channel; D017354:Point Mutation; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics
C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; C418492:KCNE3 protein, human; D062553:NAV1.4 Voltage-Gated Sodium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D019837:Ryanodine Receptor Calcium Release Channel; C106251:SCN4A protein, human; D015222:Sodium Channels