The Clinical Features And Mutation Analysis Of SCN4A Gene In A Normokalemic Periodic Paralysis Family

Objective:To report a normokalemic periodic paralysis?normoPP?family,the clinical features and mutation characteristics of SCN4A gene were discussed.Methods:The clinical manifestations and laboratory examination of patients in the family were analyzed.Peripheral blood was collected from the proband and his family members,then extracted DNA and detected the pathogenic gene through the microarray exon-capture and next-generation sequencing technology of hereditary myopathy.Results:?1?The proband?III₂?was a 52-year-old man,his main clinical manifestations were recurrent and various weakness of limbs from childhood.The most common manifestation was mild weakness that presented low-grade limbs weakness for more than half-month;however,serious attack lead to difficulty in getting up,one to two hours could be relieved;cold,fatigue etc were main predisposing factor.There was no obvious abnormality during the interval time.During the course of the disease,serum potassium levels were normal,scrum creatine kinase was 462.75 IU/L?normal range is 38-174 IU/L?;electromyography suspected as atypical myogenic damage.Muscle biopsy discovered:HE staining showed muscle fiber was slightly varied in size,scattered with small round and angular muscle fibers,no obvious necrotizing fibers and vacuolar change,with a mount of increased similar nuclei,slight hyperplasia of perimysium,and no inflammatory cell infiltration.No abnormality were found in enzyme histological and immunohistochemical staining.?2?Recurrent weakness was also observed in II₆,III₅,III₇,IV₂,IV₄ and V₁ family members,but the severity and frequency varied greatly.Among them,IV₂ member manifested the worst who suffered almost continual weakness due to the quite frequent onset.Laboratory test results of IV₂,IV₄ showed normal serum potassium and slightly elevated CK level which were 554.15IU/L and 1070.68IU/L respectively.?3?Next-generation sequencing technology revealed the heterozygous mutation of c.2111C>T in SCN4A gene of the proband?III₂?.And then II₆,III₅,III₇,IV₂,IV₄ and V₁ members in this family identified the same mutation.No other pathogenic mutations were found.Conclusion:In this normoPP family,The main clinical features were recurrent muscle weakness from childhood,with normal serum potassium and slightly elevated CK level during the course.The frequency and severity varied greatly.The pathogenic gene was a c.2111C>T heterozygous mutation in SCN4A gene.