摘要方法:对先证者进行病史和家族史询问以及详细的临床检查。应用高通量测序技术对患儿进行基因变异分析，并应用Sanger测序法对变异基因的家系分布进行验证。结果:全外显子测序结果显示先证者 RYR1基因存在c. 14591 A >C(p.Tyr4864Ser)错义变异，未见该位点变异的相关性报道；Sanger测序结果显示先证者父亲、祖父、大姑、二姑的 RYR1基因均存在c. 14591 A >C(p.Tyr4864Ser)错义变异。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南， RYR1基因c. 14591 A >C判定为可能致病变异(PM2+PM5+PP1+PP3)。 结论:RYR1基因c.14591 A >C(p.Tyr4864Ser)可能是该家系遗传学病因，基因检测有助于明确诊断。新变异的检出丰富了 RYR1基因的变异数据库。

abstractsObjective:To investigate the possible causative factors of central core disease(CCD), the clinical features of a neonatal case with CCD and five patients in the pedigree line were analyzed for RYR1 gene variant.Methods:Medical and family history inquiries and detailed clinical examinations were performed in the proband . High-throughput sequencing technology was applied to analyze the gene variant of the proband , and Sanger sequencing was applied to verify the pedigree distribution of the variant.Results:The whole exon sequencing results showed that the proband has a missense variant of c. 14591 A>C (p.Tyr4864Ser) in the RYR1 gene which was unreported previously; Sanger sequencing results showed that the father, grandfather, the eldest aunt and second aunt of the proband all carried the same variant. The c. 14591 A>C variant of RYR1 gene was predicted to be a likely pathogenic (PM2+ PM5+ PP1+ PP3) according to the American College of Medical Genetics and Genomics standards and guidelines. Conclusions:The RYR1 gene c. 14591 A >C (p.Tyr4864Ser) variant may be the genetic cause of the pedigree and genetic testing helps to clarify the diagnosis. Identification of this variant has enriched the variant spectrum of the RYR1 gene.