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 an...

Full description

Saved in:
Bibliographic Details
Published in:Neurobiology of aging 2016-02, Vol.38, p.217.e9-217.e13
Main Authors: Shi, Chang-he, Mao, Cheng-yuan, Zhang, Shu-yu, Yang, Jing, Song, Bo, Wu, Ping, Zuo, Chuan-tao, Liu, Yu-tao, Ji, Yan, Yang, Zhi-hua, Wu, Jun, Zhuang, Zheng-ping, Xu, Yu-ming
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2015.10.040