CHCHD2 gene mutations in familial and sporadic Parkinson's disease

被引：58

作者：

Shi, Chang-he ^{[1
]}

Mao, Cheng-yuan ^{[1
]}

Zhang, Shu-yu ^{[1
]}

Yang, Jing ^{[1
]}

Song, Bo ^{[1
]}

Wu, Ping ^{[2
]}

Zuo, Chuan-tao ^{[2
]}

Liu, Yu-tao ^{[1
]}

Ji, Yan ^{[1
]}

Yang, Zhi-hua ^{[1
]}

Wu, Jun ^{[1
]}

Zhuang, Zheng-ping ^{[3
]}

Xu, Yu-ming ^{[1
]}

机构：

[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurol, 1 Jian She East Rd, Zhengzhou 450000, Henan, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Huashan Hosp, PET Ctr,Dept Nucl Med, Shanghai 200433, Peoples R China

[3] NINDS, Surg Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

来源：

NEUROBIOLOGY OF AGING | 2016年 / 38卷

基金：

中国国家自然科学基金;

关键词：

CHCHD2; PET; ADPD; VARIANTS; REVEALS; NETWORK; VPS35;

D O I：

10.1016/j.neurobiolaging.2015.10.040

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Mutations in CHCHD2 gene have been reported in autosomal dominant Parkinson's disease (ADPD). However, there is still lack of evidence supported CHCHD2 mutations lead to ADPD in other populations. We performed whole exome sequencing, positron emission tomography (PET), and haplotype analyses in an ADPD pedigree and then comprehensively screened for CHCHD2 gene mutations in additional 18 familial parkinsonism pedigrees, 364 sporadic PD patients, and 384 healthy controls to assess the frequencies of known and novel rare nonsynonymous CHCHD2 mutations. We identified a heterozygous variant (c.182C>T; p.Thr61Ile) in the CHCHD2 gene in the ADPD pedigree. PET revealed a significant reduction in dopamine transporter binding in the putamen and caudate nucleus of the proband, similar to idiopathic PD. The single nucleotide variant 5C>T (Pro2Leu) in CHCHD2 was confirmed to have a significantly higher frequency among sporadic PD patients than controls. Our results confirm that ADPD can be caused by CHCHD2 mutations and show that the Pro2Leu variant in CHCHD2 may be a risk factor for sporadic PD in Chinese populations. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：217.e9 / 217.e13

页数：5