二代测序法对中央轴空病的诊断价值:附1例报告

Diagnostic value of second generation sequencing for central axis disease: a case report

目的探讨二代测序法在中央轴空病诊断中的价值。方法回顾分析1例中央轴空病患儿的临床资料,以及二代测序和多重连接探针扩增技术对致病基因检测的结果。结果患儿,女,3岁,临床表现为行走困难缓慢加重、发育迟缓、面部肌无力、先天性髋关节脱位。体格检查显示脊柱侧弯,不同程度近端肌张力及肌力减低、肌容积缩小,腱反射减弱,病理征阴性。肌酸激酶轻度升高,肌电图未见异常。应用二代测序法检测发现患儿RYR1基因存在新生的错义变异c.14582G>A,p.Arg 4861His(杂合),经Alamut功能软件预测此位点变异可能会影响蛋白结构与功能,与中央轴空病高度相关。结论国内首次报道RYR1基因变异位点c.14582G>A,p.Arg4861His。临床高度怀疑中央轴空病时可选择二代测序法确诊。

Objectives To explore the value of second generation sequencing in the diagnosis of central core disease(CCD).Methods The clinical data and the results of detection of pathogenic genes by multiplex linked probe amplification and second generation sequencing in one CCD patient were retrospectively analyzed.Results A 3-year-old girl presented slowly progressive walking difficulty,developmental retardation,facial myasthenia and congenital dislocation of hip joint.His parents had no similar clinical manifestations.Physical examination showed scoliosis,varying degrees of reduction in proximal muscle tension and muscle strength,muscle volume reduction and tendon reflex weakening,while pathological signs were negative.The patient's creatine kinase was slightly elevated and electromyography was normal.There was a novel missense mutation of c.14582G>A,p.Arg4861His(heterozygous)in the RYR1 gene detected by second generation sequencing method.The Alamut functional software predicted that the mutation could affect the structure and functions of the protein,and was highly related to CCD.Conclusion The RYR1 gene mutation of c.14582G>A,p.Arg4861His is first reported in China.The second generation sequencing method can be used for the confirmation of diagnosis of suspected CCD.