The Clinical And Gene Mutation Study In A Large Family Of Paramyotonia Congenita

Objective:To investigate the clinical festures and SCN4A gene mutation in a large family of Paramyotonia Congenita.Methods:The medical histories and clinical phenotypes of the affected members in a Paramyotonia Congenita family were collected. We also examined some items of the proband in the interictal phase, such as cardiac creatine、electrolyte、blood glucose、routine electromyography (EMG) examinations、muscle biopsies and color dopplar ultrasound of thyroid. The genetic researches of PMC patients and some immediate relatives were conducted. We extracted genomic DNA from peripheral venous blood by using routine saturated phenol-phenochloro technique, following the expanding of all the24exons of SCN4A gene in polymerase chain reaction experiments. And the expanded products were then examinated by using DNA sequence meter, at last the results were tested at the NCBI web(http://www.ncbi.nlm.nih.gov/)to determine if there were any changes in amino acid sequences, and if there were, positioning would be done.Results:There were total34people in5generations, including10patients in3generations. Both male and female were affected. All patients in the family showed typical symptoms when borned, and usually developed into muscle paralysis and stiffness once exposed to cold. And the symptoms were not serious, and improved a lot when they got into adultery. The patients only showed little postive signs when they were physically examined, such as mild hypermyotrophy or muscles contracting like balls when they exerted their strengthes. Cold water inducing experiments proved effective. The proband had normal blood convention, hemagglutination inspection, fasting blood sugar, electrocardiogram, chest radiograph and color dopplar ultrasound of thyroid. The creatine kinase was244.1U/L, a little higher than normal. Interestingly, the proband has low serum potassium electrolytes twice(3.47mmol/L,3.38mmol/L,for each).The routine electromyography showed myotonic discharges in the deltoids、biceps muscles rachioradialis、vastus medialis and tibialis anterior muscles, gastrocneius muscles, which summed up to reach pathological interference stage. Moderate muscle contractions produced more shorrt、spike potentials in motor units. Electroneurography showed no abnormalities. It suggested myopathtic damages in upper and lower limbs (They showed myotonic discharges). Muscular biopsy showed scattered muscle fibers atrophy, and some of them dismatched as angle forms. The muscle nuclei seemed to increase. And nuclear translocation existed. We sequenced all the24exons of the SCN4A gene of the affected in the family. We found a doublepeak at3938, which was a missence mutation leading to a C-to-T replacement. This yielded a positive result, that was, a mostly-described mutation SCN4A p.Thr1313Met exon22(T1313M) in the linker between domain III and domain IV of sodium channel gene, which was detected in all of the patients from the family. while mutations were absent from other encoding areas of the SCN4A gene. The unaffected members of the PMC family revealed no mutation after sequencing of the same hot spot of SCN4A gene.Conclusions:1. The family is characterized by cold-induced myotonia and muscle stiffness from early childhood, muscle hypertrophy by physical examination, myotonic discharges in the electromyography accompanied by changes in blood potassium. The disease is inherited by autosomal dominant pattern.2.Genetic screening shows that the family is caused by sodium channel gene mutations, and verifies Thr1313Met (T1313M) mutation on the22nd exon of SCN4A gene, which is consistent with foreign literatures reported before. It reveals the PMC family doesn’t harbor new mutations.