Identification Of Ascn4amutation In A Large Chinese Family With Atypical Normokalemic Periodic Paralysis Using Whole-Exome Sequencing

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 ofSCN4Ain a Chinese family segregating for NormoKPP. Results Whole-exome sequencing revealed a c.2111C>T substitution inSCN4Ain 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 inSCN4Ain NormoKPP, and provide information about the relationship between genotype and atypical clinical symptoms.