PRRT2基因新发移码突变导致发作性运动诱发性运动障碍的家系分析

Analysis of a novel frame-shift mutation of PRRT2 gene in a pedigree with paroxysmal kinesigenic dyskinesia

目的报道1例表现为发作性运动诱发性运动障碍(PKD)的家系,对其富含脯氨酸的跨膜蛋白2(PRRT2)的基因进行分析,探讨其致病原因。方法收集该家系成员的临床资料,对先证者及核心家系成员PRRT2基因编码区进行Sanger测序分析。结果在该家系中,除先证者符合PKD临床诊断外,其舅舅幼儿期曾患“癫痫”,7岁后不治而愈;其姨表哥在婴儿期曾有“惊厥”发作。基因检测结果显示,该先证者及其表型正常的母亲PRRT2基因出现1个移码突变c.498delC(p.Thr167Profs*9)。该位点目前人类基因突变数据库中尚未报告,属新发突变位点。结论该先证者PKD症状与PRRT2基因c.498delC突变有关。在该家系出现的不同表型甚至表型正常,可能由于基因外显不全有关。我们推测c.498delC突变导致了PRRT2基因表达的蛋白被截短,影响了该蛋白的跨膜区而致病。

Objective To analyze the clinical data of a patient with paroxysmal kinesigenic dyskinesia(PKD)and his family members and the gene expression of proline-rich transmembrane protein 2(PRRT2),and to explore the possible pathogenesis of PKD.Methods The clinical data of the family members was collected and the PRRT2 genes of the proband and core family members were analyzed by Sanger sequencing.Results In the pedigree,the proband met the clinical diagnosis standards of PKD,while his uncle had suffered from"epilepsy"in childhood and recovered after 7 years old;and his cousin presented"convulsion"in his infancy.The genetic test results showed a frame-shift mutation c.498delC(p.Thr167Profs*9)in the PRRT2 gene of the proband and his mother with normal phenotype.At present,such a mutation has not been reported in the Human Gene Mutation Database,which is a novel mutation site.Conclusions The symptoms of PKD in this proband is related to c.498delC mutation of the PRRT2 gene.There may be different or even normal phenotypes in the same family,due to incomplete penetrance of the gene.It is speculated that c.498delC mutation results in the truncated protein of PRRT2 gene,which affects the transmembrane region of the protein.