Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia

• Published in: Muscle & nerve 2004-07, Vol.30 (1), p.114-117
• Main Authors: Marchant, Clare L., Ellis, F. Richard, Halsall, P. Jane, Hopkins, Philip M., Robinson, Rachel L.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Calcium Channels - genetics; dihydropyridine receptor; Diseases of striated muscles. Neuromuscular diseases; DNA Mutational Analysis; Humans; hypokalemic periodic paralysis; Hypokalemic Periodic Paralysis - genetics; Male; malignant hyperthermia; Malignant Hyperthermia - genetics; Medical sciences; NAV1.4 Voltage-Gated Sodium Channel; Neurology; Point Mutation; Potassium Channels - genetics; Potassium Channels, Voltage-Gated; ryanodine receptor; Ryanodine Receptor Calcium Release Channel - genetics; Sodium Channels - genetics
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.20068

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. Muscle Nerve 30: 114–117, 2004