Identification of a SCN4A mutation in a large Chinese family with atypical normokalemic periodic paralysis using whole-exome sequencing

Abstract

Objectives Normokalemic periodic paralysis (NormoKPP) of skeletal muscle is an autosomal dominant disorder caused by mutations in the gene encoding voltage-gated sodium channel protein type 4 subunit alpha ( SCN4A), which leads to ion channel dysfunction. Little is known about the relationship between genotype and the clinical symptoms of NormoKPP. The present study aimed to evaluate the genetic variation in a large Chinese family with NormoKPP. The patients in this pedigree did not respond to saline treatment, but calcium gluconate treatment was effective. Methods We performed a series of clinical examinations and genetic analyses, using whole-exome and Sanger sequencing, to examine the mutation status of SCN4A in a Chinese family segregating for NormoKPP. Results Whole-exome sequencing revealed a c.2111C>T substitution in SCN4A in most of the affected family members. This mutation results in the amino acid substitution p.T704M. Conclusions These results support a causative role of this mutation in SCN4A in NormoKPP, and provide information about the relationship between genotype and atypical clinical symptoms.