一例Charcot-Marie-Tooth病4F型患儿的PRX基因变异分析

Analysis of PRX gene variants in a child with Charcot-Marie-Tooth disease type 4F

目的对1例临床怀疑为腓骨肌萎缩症的患儿进行基因变异分析,明确其可能的遗传学病因。方法应用二代测序技术,对该家系进行分子遗传学分析。结果测序结果显示患儿PRX基因(NM_181882)存在c.52G>T(p.Glu18X)和c.1390C>T(p.Arg464X)复合杂合变异,患儿父亲携带c.52G>T杂合变异,母亲携带c.1390C>T杂合变异,表明患儿的2个变异分别遗传自父亲和母亲,c.52G>T为未报道过的新变异。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,c.52G>T(p.Glu18X)和c.1390C>T(p.Arg464X)均被判定为致病性变异(PVS1+PM2+PM3,PVS1+PM3-Strong+PM2+BS2)。结论PRX基因c.52G>T(p.Glu18X)和c.1390C>T(p.Arg464X)复合杂合变异可能是患儿的致病原因,新变异的检出丰富了PRX基因变异谱。

Objective To explore the genetic etiology of a child suspected for peroneal muscular atrophy.Methods The child and his parents were analyzed by using next generation sequencing.Results The child was found to harbor compound heterozygous variants of c.52G>T(p.Glu18X)and c.1390C>T(p.Arg464X)of the PRX gene,which were inherited from his father and mother,respectively.Among these,the c.52G>T variant was previously unreported.Based on the standards and guidelines of the American College of Medical Genetics and Genomics,both variants were predicted to be pathogenic(PVS1+PM2+PM3,PVS1+PM3-Strong+PM2+BS2).Conclusion The compound heterozygous variants of the PRX gene probably underlay the Charcot-Marie-Tooth disease type 4F in this child.Above finding has enriched the mutational spectrum of the PRX gene.