PRRT2基因表现帕金森样症状的老年发作性运动诱发性运动障碍家系研究

A pedigree study of paroxysmal exercise-induced dyskinesia with Parkinson-like symptoms associated with the expression of the PRRT2gene in the elderly

目的研究家族性以帕金森样临床表现的老年发作性运动诱发性运动障碍临床及遗传学特点。方法对9个家系成员的临床资料进行分析,包括2例患者(2例均经过治疗),并允许进行相应的治疗和预测。从外周血样中提取DNA,然后进行二代测序突变筛查。结果在家系中两例先证者经奥卡西平治疗震颤完全控制,在5例家族成员中发现PRRT2基因16号染色体29824741位置2号外显子c.G366C号:P.QCon122H发生碱基G>C杂合突变,导致编码的122号氨基酸由谷氨酸变异为组胺酸,经SIFT和M-CAP等预测有害。家系样本Sanger测序显示先证者之妹妹、弟弟及侄子为杂合型变异,其侄女为野生型。结论PRRT2蛋白的Q122可引起帕金森样肢体震颤表型,抗癫痫药物对老年发作性运动诱发性运动障碍也有效。

Objective To study the clinical and genetic characteristics of familial paroxysmal exercise-induced dyskinesia with Parkinson-like manifestations in the elderly.Methods Clinical data of 9 family members were analyzed,including 2 patients(both received treatment)consenting to appropriate therapy and prediction protocols.DNA was extracted from peripheral blood samples,and then second-generation sequencing mutation screening.Results The tremor of two probands in the family was completely brought under control by oxcarbazepine treatment.In 5 family members,a heterozygous mutation of base G>C in exon 2 c.G366C:P.QCon122H at position 29824741 of the PRRT2 gene was found,resulting in the mutation of the amino acid at 122 from glutamine to histidine,which was predicted by SIFT and M-CAP to be harmful.Sanger sequencing of pedigree samples showed that the sisters,brothers and nephews of the proband were heterozygous and their nieces were of the wild type.Conclusions Q122 of PRRT2 protein can cause the Parkinson-like limb tremor phenotype,and antiepileptic drugs are also effective for paroxysmal exercise-induced dyskinesia in the elderly.