Mutation (Thr704Met) of the SCN4A gene causes severe familial hypokalemic periodic paralysis

Objective To investigate the clinical features and pathogenic genes of a familial hypokalemic periodic paralysis (HOKPP). Methods PCR amplification and DNA sequencing were used to screen candidate genes of the HOKPP family members (CACNA1S, SCN4A, KCNE3), and the clinical features were carefully analyzed at the same time. Results The sequencing analyses of the SCN4A gene in the proband identified three nucleotide sequence mutations, which influenced the amino acid sequence of the skeletal sodium channel. One of the mutations was identified as a C/T heterozygous pattern at the 2111th nucleotide position in exon 13, resulting in a change from Thr to Met at the 704th amino acid position of the sodium channel protein. All affected patients carried the Thr704Met mutation, whereas unaffected family members did not. Clinical symptoms in this family followed an autosomal dominant inheritance pattern. Muscles weakness, pain and hypokalemia in the period between attacks were seen in all patients. Paralytic symptoms occurred early, lasted longer and recurred frequently, while cold was the main predisposing factor. With the progress of the disease, patients represented persistent weakness and atrophy in proximal muscles. Conclusions Mutation (Thr704Met) in the SCN4A gene should be responsible for this family. This mutation causes severe HOKPP and progressive muscle atrophy. Key words: Hypokalemic periodic paralysis; Nav1.4 voltage-gated sodium channel; DNA mutational analysis; Muscular atrophy