伴神经系统损害的Perrault综合征患者的临床表型及基因变异分析  

Clinical and genetic analysis of a patient with Perrault syndrome and additional neurological features

作　　者：段晓慧[1] 汪伟[1] 董明睿[1] 王璐[1] 邵自强[1] 王朝霞[2] 袁云[2] 汪仁斌[1] 彭丹涛[1] Duan Xiaohui;Wang Wei;Dong Mingrui;Wang Lu;Shao Ziqiang;Wang Zhaoxia;Yuan Yun;Wang Renbin;Peng Dantao(Department of Neurology,China-Japan Friendship Hospital,Beijing 100029,China;Department of Neurology,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]中日友好医院神经内科,北京100029 [2]北京大学第一医院神经内科,100034

出　　处：《中华医学遗传学杂志》2019年第6期577-580,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(8170051712).

摘　　要：目的 对1例伴有神经系统损害的Perrault综合征患者进行TWNK基因变异分析,明确其致病原因.方法 应用高通量测序及Sanger测序法对患者TWNK基因进行变异分析.结果 高通量测序结果显示患者TWNK基因存在c.794G>A(p.Arg265His)和c.1181G>A (p.Arg394His)杂合变异;Sanger测序验证结果显示患者TWNK基因存在c.794G>A(p.Arg65His)和c.1181G>A(p.Arg394His)复合杂合变异,其父亲携带c.1181G>A(p.Arg394His)杂合变异,母亲携带c.794G>A(p.Arg265His),因此患者的变异分别来自父母.其中,c.1181G>A(dbSNP:rs752211501)为已报道的致病性变异;c.794G>A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基因变异分类标准,为可能的致病突变.结论 Perrault综合征患者可伴有神经系统多部位损害,TWNK基因c.794G>A(p.Arg265His)和c.1181G>A(p.Arg394 His)复合杂合变异可能为患者的致病原因.Objective To explore the clinical,neuropathological and genetic characteristics of a patient with Perrault syndrome caused by TWNK mutation.Methods Potential variation of the TWNK gene was detected by next generation sequencing and verified by Sanger sequencing.Results The patient has featured primary amenorrhoea and progressive sensorineural hearing loss since childhood.She also had gait anormaly,distal limb atrophy and weakness,and nystagmus.Further study confirmed sensory neuronopathy accompanied with upper and lower motor neuron involvement as well as cerebellum atrophy.Next generation sequencing has identified two heterozygous variants of the TWNK gene,namely c.794G>A(p.Arg265His)and c.1181G>A(p.Arg394His).Sanger sequencing confirmed that c.1181G>A(p.Arg394His),a known pathogenic variant,was derived from her farther,while c.794G>A(p.Arg265His),a novel variant,was derived from her mother and likely pathogenic according to the ACMG guidelines.Conclusion Perrault syndrome is a group of disorders with a high phenotypic heterogeneity.The compound heterozygous variation of c.794G>A(p.Arg265His)and c.1181G>A(p.Arg394His)of the TWNK gene may underlie Perrault syndrome in the patient.

关 键 词：Perrault综合征 遗传性周围神经病 TWNK基因 感觉神经元病 小脑萎缩 

分 类 号：R5[医药卫生—内科学]