一例新生儿中央轴空病的临床特点及家系基因变异分析

Clinical characteristics and genetic analysis of a pedigree affected with neonatal central core disease

对1例新生儿中央轴空病的临床特点及家系中5例患者进行RYR1基因变异分析,明确其可能的致病原因。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。

Objective 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.