Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica.
OBJECTIVE
Patients with paralysis periodica paramyotonica exhibit a clinical syndrome with characteristics of both hyperkalaemic periodic paralysis and paramyotonia congenita. In several types of periodic paralysis associated with hyperkalaemia, mutations in the skeletal muscle sodium channel (SCN4A) gene have been previously reported. Phenotypic variations of mutations in SCN4A, however, have not been described yet. The present study aimed to evaluate genetic variations in a family with clinical and electrophysiological characteristics of paralysis periodica paramyotonia.


METHODS
Seven members of a family affected with symptoms of paralysis periodica paramyotonia were studied by electrophysiological and genetic analyses. There were increased serum potassium concentrations in four members during paralytic attacks induced by hyperkalaemic periodic paralysis provocation tests. Short exercise tests before and after cold immersion were carried out in four patients to distinguish electrophysiological characteristics of hyperkalaemic periodic paralysis and paramyotonia. Sequencing analyses of SCN4A were performed on one patient and a normal control to identify polymorphisms. Restriction fragment length polymorphism (RFLP) analysis was then performed at the identified polymorphic sites.


RESULTS
Electrophysiological studies showed both exercise sensitivity and temperature sensitivity. Compound motor action potential (CMAP) amplitudes were decreased (7.3%-28.6%) after short exercise tests. The CMAP amplitudes were even more severely decreased (21.7%-56.5%) in short exercise tests after cold exposure. Three polymorphic sites, Gln371Glu, Thr704Met, and Aspl376Asn were identified in SCN4A. RFLP analyses showed that all affected patients carried the Thr704Met mutation, whereas unaffected family members and a normal control did not.


CONCLUSIONS
Phenotypic variation of the Thr704Met mutation, which was previously reported in patients with hyperkalaemic periodic paralysis, is described in a family affected with paralysis periodica paramyotonia.
Kim
J
J
Department of Neurology, College of Medicine, Chungnam National University, 640 Daesa-dong, Joong-ku, Taejon, Korea.
Hahn
Y
Y
Sohn
E H
EH
Lee
Y J
YJ
Yun
J H
JH
Kim
J M
JM
Chung
J H
JH
D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004576:Electromyography; D006801:Humans; D007723:Korea; D009132:Muscles / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D062553:NAV1.4 Voltage-Gated Sodium Channel; D020513:Paralysis, Hyperkalemic Periodic / Q000235:genetics* / Q000503:physiopathology*; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D015222:Sodium Channels / Q000235:genetics*
D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels