[P3-129] Gene Diagnosis of one Central Core Disease Pedigree by the Next-Generation Sequencing
[Introduction] We applied next generation sequencing (NGS) to diagnose one suspected case, and to evaluate the value of NGS in the diagnosis of central core disease. [Methodology] We collected three milliliter peripheral blood samples of the patient and his parents to detected pathogenic gene by NGS. [Results] The clinical manifestations of the patient were slowly progressive difficulty walking, developmental delay, facial muscle weakness, congenital dislocation of the hip joint, and his parents had no similar clinical manifestations. The physical examination showed scoliosis, different degrees of proximal muscle tension and muscle strength decrease, the volume of the muscle contraction, the decreased of tendon reflex, and the pathological sign was negative. Slight elevation of creatine kinase and normal EMG. 2742 disease-related genes were detected by NGS, then trap exon by Agilent SureSelect method and high-throughput sequencing by Illumina sequencing platform. NextGENe software was applied for data analysis and Ingenuity online system was applied for variation screening and interpretation. A novel missense mutation (NM-000540.2) "c.14582G>A p.Arg4861His (heterozygous) of RYR1 gene was found in our patient. Alamut software predicted this mutation may affect the protein structure and function, and highly related to the central core disease. Parents had no similar symptoms or mutations. So the mutation is a de novo mutation which can be determined as the pathogenic mutation. The boy’s parents refused to have a muscular biopsy for his child. [Conclusions] NGS detection has an important role in guiding the selection of further biopsy. NGS should be firstly tested in patients with clinical suspected central core disease.