title: The heterozygous R1441C mutation of leucine-rich repeat kinase 2 gene in a Chinese patient with Parkinson disease: A five-year follow-up and literatures review.
abstract: BACKGROUND
  Leucine-rich repeat kinase 2 gene (LRRK2) was recognized associated with both familial and sporadic Parkinson Disease (PD). Seven missense mutations (G2019S, R1441C, R1441G, R1441H, Y1699C, I2020T, N1437H) of it have been confirmed disease- causing. They were common among Caucasian PD patients, but rarely reported in Asian, especially in Chinese Han population.
  
  
  OBJECTIVE
  We aimed to identify the frequencies of these seven mutations of LRRK2 in Chinese early-onset PD (EOPD) patients and analyze the phenotypes.
  
  
  METHODS
  One hundred and thirty seven EOPD patients were enrolled for genetic testing. The seven disease-causing mutations of LRRK2 were carried out by target sequencing using Illumina HiSeq 2000 Sequencer. The identified variants were further confirmed by Sanger sequence. The clinical materials were investigated retrospectively.
  
  
  RESULTS
  Only one patient (0.73%) was found carrying pathogenetic LRRK2 mutation of R1441C. The age at onset of the female patient was 44. She manifested typical motor symptoms of PD and responded well to levodopa therapy. Longitudinal evaluation showed progression of motor symptoms and depression but no cognitive impairment. The dopamine transporter (DAT) imaging via [11C]-2β-carbomethoxy-3β-(4-fluorophenyl) tropan (CFT) and Positron emission computed tomography (PET) revealed typical dopamine transporter uptake reduction.
  
  
  CONCLUSIONS
  The LRRK2 R1441C mutation was found in a Chinese EOPD patient for the first time. The manifestations of LRRK2-R1441C carriers were indistinguishable from sporadic PD patients.
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Sun
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
authors.forename: Su-Shan
authors.initials: SS
authors.lastname: Luo
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
authors.forename: Da-Ke
authors.initials: DK
authors.lastname: Li
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
authors.forename: Yi-Xuan
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
authors.forename: Feng-Tao
authors.initials: FT
authors.lastname: Liu
authors.affiliation: PET Center, Huashan Hospital, Fudan University, 518 East Wuzhong Road, Shanghai 200235, China.
authors.forename: Chuan-Tao
authors.initials: CT
authors.lastname: Zuo
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China.
authors.forename: Zheng-Tong
authors.initials: ZT
authors.lastname: Ding
authors.affiliation: Institute of Biomedical Sciences, Medical School, Fudan University, 131 Dongan Road, Shanghai 200032, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: An
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China. Electronic address: wujianjun@fudan.edu.cn.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Department & Institute of Neurology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China. Electronic address: wangjian336@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics; D002681:China; D005500:Follow-Up Studies; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D009154:Mutation; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Dopamine transporter imaging; Early-onset PD; Leucine-rich repeat kinase 2 gene; Parkinson disease; Positron emission computed tomography; R1441C mutation