Objectives-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 aVected patients carried the Thr704Met mutation, whereas unaVected family members and a normal control did not. Conclusion-Phenotypic variation of the Thr704Met mutation, which was previously reported in patients with hyperkalaemic periodic paralysis, is described in a family aVected with paralysis periodica paramyotonia. (J Neurol Neurosurg Psychiatry 2001;70:618-623) Keywords: paralysis periodica paramyotonica; hyperkalaemic periodic paralysis; paramyotonia congenita; human skeletal muscle sodium channel (SCN4A) gene Patients with periodic paralysis exhibit recurrent episodes of skeletal muscle weakness followed by complete recovery.

The KEM1/XRN1 gene was originally identified because of its functions in microtubule-mediated processes, and is also known to be a major cytoplasmic 5P-3P exoribonuclease gene, which is involved in RNA turnover. Here we present evidence that KEM1 plays a role in filamentous growth. In Saccharomyces cerevisiae, the filamentation signalling shares multiple components of the MAP kinase cascade (STE7, STE11, and KSS1) and the transcription factor STE12 with mating process. Both haploid invasive growth and diploid pseudohyphal growth were found to be greatly impaired in kem1 mutant strains. KEM1 affected the level of FLO11 transcripts and the expression of the filamentation-associated reporter genes, Ty1-lacZ and FLO11-lacZ. Suppression analysis implies that KEM1 does not affect the RAS/PKA pathway, but that it possibly functions downstream of the MAP kinase pathway during filamentation.

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