Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica

Objectives-Patients with paralysis periodica paramyotonica exhibit st clini cal syndrome with characteristics of both hyperkalaemic periodic paralysis and paramyotonia congenita. In several types of periodic paralysis associat ed with. hyperkalaemia. mutations in the skeletal muscle sodium channel (SC N4A) gene la ve been previously reported, Phenotypic variations of mutation s in SCN4A, however, have not been described Set. The present study aimed t o evaluate genetic variations in a family with clinical and electrosphysiol ogical characteristics of paralysis periodica paramyotonia. Methods-Seven members of a family affected with symptoms of paralysis perio dica paramyotonia were studied by electrophysiological and genetic analyses , There were increased serum potassium concentrations in four members durin g paralytic attacks induced by hyperkalaemic periodic paralysis provocation tests. Short exercise tests before and after cold immersion were carried o ut in four patients to distinguish electrophysiological characteristics of hyperkalaemic periodic paralysis and paramyotonia. Sequencing analyses of S CN4A were performed an one patient and a normal control to identify polymor phisms, Restriction fragment length polymorphism (RFLP) analysis was then p erformed at the identified polymorphic sites. Results-Electrophysiological studies showed both exercise sensitivity and t emperature sensitivity. Compound motor action potential (CMAP) amplitudes w ere decreased (7.3%-25.6%) after short exercise tests. The CMAP amplitudes were even more severely decreased (21.7%-56.5%) in short exercise tests aft er cold exposure. Three polymorphic sites, Gln371Glu, Thr704Met, and Asp137 6Asn were identified in SCN4A. BP;LP analyses showed that all affected pati ents carried the Thr704Met mutation, whereas unaffected family members and a normal control did not. Conclusion- Phenotypic variation of the Thr784Met mutation, which was previ ously reported in patients with hyperkalaemic periodic paralysis, is descri bed in a family affected with paralysis periodica paramyotonia.