Negative results Mutation analysis of CHCHD2 gene in Chinese Han familial essential tremor patients and familial Parkinson’s disease patients Chao Gao a, b,1 , Yi-Meng Chen a, c,1 , Qian Sun a , Ya-Chao He a , Pei Huang a , Tian Wang a , Dun-Hui Li a , Liang Liang a , Jun Liu a , Qin Xiao a , Sheng-Di Chen a, b, c, * a Department of Neurology and Collaborative Innovation Center for Brain Science, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China b School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China c Laboratory of Neurodegenerative Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China article info Article history: Received 17 August 2016 Received in revised form 2 September 2016 Accepted 1 October 2016 Keywords: CHCHD2 Familial ET ADPD Variants Chinese abstract CHCHD2 is the latest identified Parkinson’s disease (PD)-causing gene, and previous studies have re- ported the same CHCHD2 variant (182C>T, Thr61Ile) in both PD and essential tremor (ET) patients. Whether CHCHD2 gene mutations are involved in both of these diseases remains unclear. We sequenced CHCHD2 gene in 171 familial ET patients, 133 autosomal dominant Parkinson’s disease patients, and 211 normal controls. No pathogenic mutations were found, suggesting that CHCHD2 gene may not play a major role in our familial Chinese Han ET and PD patients. Ó 2016 Elsevier Inc. All rights reserved. 1. Introduction There have been several evidences demonstrating associations between essential tremor (ET) and Parkinson’s disease (PD) including clinical, epidemiologic, imaging, and genetic studies (Thenganatt and Jankovic, 2016). CHCHD2 is the latest identified PD-causing gene and 2 previous studies have reported the same CHCHD2 variant (182C>T, Thr61Ile) in both PD and ET patients (Funayama et al., 2015; Shi et al., 2016). It raised a question of whether CHCHD2 gene mutations are involved in both PD and ET, or ET happens to coincide with PD in the same family. Nonetheless, there is no report of mutation analysis of CHCHD2 gene in ET pa- tients until now. In this study, we sequenced CHCHD2 gene in fa- milial ET patients, autosomal dominant Parkinson’s disease (ADPD) patients, and normal controls, which will address the possible in- fluence of CHCHD2 variants on the risk of ET and potential genetic link between ET and PD. 2. Methods About 171 familial ET,133 ADPD, and 221 healthy controls were recruited. None of the subjects were from consanguineous families. Patients who had affected first-degree family members in at least 2 consecutive generations (including the Proband) are defined as autosomal dominant inherited patients. Clinical diagnosis of ET and PD was confirmed by 2 or more experienced movement disorder specialists according to consensus criteria for ET and PD. Basic in- formation about the clinical cohorts were collected (Supplementary Table 1). Genotypic and allelic distribution among ET, PD, and normal control groups were compared by Pearson chi-squared test and Fisher’s exact test. 3. Results Sequencing 171 familial ET patients identified a novel variant (51-2T>A) in splice region and other 4 noncoding variants while no coding mutations were found (Fig. 1). There was no statistical difference in allelic distribution between ET group and normal controls among these variants (Supplementary Table 2). In the * Corresponding author at: Department of Neurology, Ruijin Hospital, 197 Ruijin Er Road, Shanghai, P.R. China. Tel.: þ86-021-6645-7249; fax: þ86-021-6445-4473. E-mail address: chen_sd@medmail.com.cn (S.-D. Chen). 1 Chao Gao and Yi-Meng Chen contributed equally to this work as co-first author. Contents lists available at ScienceDirect Neurobiology of Aging journal homepage: www.elsevier.com/locate/neuaging 0197-4580/$ e see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.neurobiolaging.2016.10.001 Neurobiology of Aging xxx (2016) 1.e1e1.e3