CHCHD2 gene mutations in familial and sporadic Parkinson's disease
CHCHD2 gene mutations in familial and sporadic Parkinson's disease
复制标题
家族性和散发性帕金森病的 CHCHD2 基因突变
DOI：
10.1016/j.neurobiolaging.2015.10.040
复制
发表时间：
2016-02-01
影响因子：
4.2
通讯作者：
Xu，Yu-ming
中科院分区：
文献类型：
--
作者：
Shi，Chang-he;Mao，Cheng-yuan;Xu，Yu-ming
常染色体显性帕金森病（ADPD）中有chchd2基因突变的报道。然而，仍然缺乏证据支持chchd2突变在其他人群中导致ADPD。我们对一个ADPD家系进行了全外显子组测序、正电子发射断层扫描（PET）和单倍型分析，然后在另外18个家族性帕金森家系、364名散发性PD患者和384名健康对照中全面筛选chchd2基因突变，以评估已知和新的罕见非同义schchd2突变的频率。我们在ADPD家系的hchd2基因中发现了一个杂合变异（c.182C>T; p.Thr61Ile）。PET显示先证者壳核和尾状核中多巴胺转运体结合显著减少，与特发性PD相似。证实了chchd2中单核苷酸变异5C >t （Pro2Leu）在散发性PD患者中的频率明显高于对照组。我们的研究结果证实了ADPD可能是由chchd2突变引起的，并表明chchd2中的Pro2Leu变异可能是中国人群中散发性PD的一个危险因素。
Mutations inCHCHD2gene have been reported in autosomal dominant Parkinson's disease (ADPD). However, there is still lack of evidence supportedCHCHD2mutations 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 forCHCHD2gene mutations in additional 18 familial parkinsonism pedigrees, 364 sporadic PD patients, and 384 healthy controls to assess the frequencies of known and novel rare nonsynonymousCHCHD2mutations. We identified a heterozygous variant (c.182C>T; p.Thr61Ile) in theCHCHD2gene 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) inCHCHD2was confirmed to have a significantly higher frequency among sporadic PD patients than controls. Our results confirm that ADPD can be caused byCHCHD2mutations and show that the Pro2Leu variant inCHCHD2may be a risk factor for sporadic PD in Chinese populations.