SCN4A 유전자의 엑손말단 접합위치변이에 의한 선천성 이상근긴장증 환자가족 증례보고
A novel essential splice site mutation in the SCN4A gene in a Korean family with paramyotonia congenital
Abstract
The nondystrophic myotonias and periodic paralyses are an important group of genetic muscle diseases characterized by dysfunction of ion channels that regulate cell membrane excitability. Mutations in SCN4A are associated with a spectrum of heterogeneous groups of overlapping myotonic/periodic paralysis syndromes including paramyotonia congenital, potassium-aggravated myotonia, and hyperkalemic periodic paralysis. Most disease-associated mutations in SCN4A were heterozygous missense mutations. To date, there is one case report of disease association mutation in consensus splice site. We describe the clinical and genetic features of a Korean family with paramyotonia congenital. Three members of this family were affected. The proband, 8 years-old girl had several episodes of generalized weakness and stiffness with transient mild elevations in CK and potassium levels. All affected patients showed eye closure and limb paramyotonia which increased by exposure to the cold. Examination of affected patients showed grip myotonia. Needle electromyography recording showed spontaneous myotonic discharges, motor unit potentials and abnormal early recruitment in predominantly proximal limb muscles. A novel heterozygous mutation of c.3911_3912+1dupAGA in SCN4A was identified using family whole exome sequencing by the Illumina NextSeq500 platform (Illumina Inc., San Diego, USA). The mutation is located on essential splice site around the boundary between exon 21 and intron 21 of SCN4A gene. We report an autosomal dominant inherited novel SCN4A mutation in essential splicing site in family with paramyotonia congenital. Our observation provides a new insight into the genotype-phenotype correlation in sodium channelopathies.