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. 2020 Sep;48(9):300060520953643.
doi: 10.1177/0300060520953643.

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

XinYu Tan  1 , SongNian Hu  1 , Zongyu Xie  2 , Hailiang Mei  1 , Yang Liu  3 , Liang Yin  3 , Peng Shi  3 , Qiming Chen  3 , Daoqian Sang  3
Affiliations

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

XinYu Tan et al. J Int Med Res. 2020 Sep.

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.

Keywords: Normokalemic periodic paralysis; SCN4A; Sanger sequencing; ion channel; mutation; whole-exome sequencing.

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Figures

Figure 1.
Figure 1.
Family pedigree. Black symbols, affected individuals; open symbols, unaffected individuals; square, male; circle, female; question mark, unknown phenotype; ⊥ non-offspring; ⨼⨽ lost to follow-up; slash, deceased individuals; arrow, proband.
Figure 2.
Figure 2.
SCN4A mutation detection in a family with normokalemic periodic paralysis (NormoKPP). (a) Pedigree structure of a NormoKPP family carrying the c.2111C>T mutation in SCN4A. (b) SCN4A DNA sequencing results of a patient and a healthy control.
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