一个PARK2基因复合杂合突变导致的帕金森病家系的遗传学研究  

Genetic study of a Parkinson's disease pedigree caused by compound heterozygous mutations in PARK2 gene

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作  者:陈美红 岑志栋[2] 陈悠[2] 郑晓省 谢非[2,3] 陈思 罗巍 Chen Meihong;Cen Zhidong;Chen You;Zheng Xiaosheng;Xie Fei;Chen Si;Luo Wei(Department of Neurology,Tiantai People's Hospital,Tiantai,Zhejiang 317200,China;Department of Neurology,the Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310000,China;Department of Neurology,Sir Run Run Shaw Hospital ,School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310000,China;Intensive Care Unit,Zhejiang Hospital,Hangzhou,Zhejiang 310012,China)

机构地区:[1]浙江省天台县人民医院神经科,317200 [2]浙江大学医学院附属第二医院神经科,杭州310009 [3]浙江大学医学院附属邵逸夫医院神经科,杭州310009 [4]浙江医院重症医学科,杭州310012

出  处:《中华医学遗传学杂志》2018年第6期815-818,共4页Chinese Journal of Medical Genetics

基  金:国家自然科学基金(81571089,81371266,81600850).

摘  要:目的明确1个兄弟3人患病的帕金森病家系的致病突变。方法收集所有患者及家系成员的外周血DNA及RNA,综合应用多重连接探针扩增及下一代测序技术检测帕金森病的致病突变。对所发现的剪接位点突变,用患者RNA逆转录而成的cDNA进行验证。结果多重连接探针扩增发现先证者存在PARK2基因第3外显子杂合缺失。下一代测序发现先证者存在PARK2基因第6外显子上游3个碱基处1处剪接位点突变(c.619-3G>C),并通过Sanger测序证实。cDNA样本测序证实c.619-3G>C造成第6外显子剪接异常,同时也证实两个突变在家系内均与疾病共分离。结论该家系为PARK2基因复合杂合突变致病。c.619-3G>C突变可导致第6外显子剪接异常,丰富了PARK2基因的致病突变谱。Objective To explore the genetic basis for a Chinese pedigree where three siblings were affected with Parkinson's disease.Methods Multiple ligation-dependent probe amplification (MLPA)and next-generation sequencing (NGS)were employed to detect the causative mutation.Sanger sequencing of cDNA was also used for verify the effect of mutation on the transcription of RNA.Results Heterozygous deletion of exon 3 of the PARK2gene was detected by MLPA,while a heterozygous splice site variant c.619-3G>C was detected by NGS.Both mutations were shown to result in aberrant transcripts of the PARK2 gene (loss of exons 3 and 6,respectively)by Sanger sequencing of cDNA.Both mutations have cosegregated with the disease in the pedigree.Conclusion Compound heterozygous mutations of the PARK2 gene probably underlie the disease in this pedigree.Identification of the splice site variant c.619-3G>C has expanded the mutation spectrum of the PARK2 gene.

关 键 词:帕金森病 PARK2基因 外显子缺失 剪接位点突变 复合杂合突变 

分 类 号:R114[医药卫生—卫生毒理学;医药卫生—公共卫生与预防医学]

 

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