title: CHCHD2 gene mutations in familial and sporadic Parkinson's disease.
abstract: 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.
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Chang-He
authors.initials: CH
authors.lastname: Shi
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Mao
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: PET Centre, Department of Nuclear Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: PET Centre, Department of Nuclear Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Chuan-Tao
authors.initials: CT
authors.lastname: Zuo
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yu-Tao
authors.initials: YT
authors.lastname: Liu
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Yang
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Zhuang
authors.affiliation: Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China. Electronic address: xuyuming@zzu.edu.cn.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Xu
mesh_terms: D002421:Caudate Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059472:Exome / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D056726:Genetic Association Studies; D006239:Haplotypes; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D011699:Putamen / Q000378:metabolism; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C580880:CHCHD2 protein, human; D004268:DNA-Binding Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors
keywords: ADPD; CHCHD2; PET