title: PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort.
abstract: OBJECTIVE
  Mutations in the PLA2G6 gene at the PARK14 locus have been reported in complicated parkinsonism. To assess the prevalence of and phenotypes associated with PLA2G6 gene mutations, we screened PLA2G6 mutations in a cohort of patients with autosomal recessive early-onset parkinsonism (AREP).
  
  
  METHODS
  We selected 12 families with AREP in which the Parkin, PINK1, DJ-1, ATP13A2, and FBXO7 gene mutations had been previously excluded. All patients came from the mainland of China. The entire PLA2G6 coding region and exon-intron boundaries were sequenced from genomic DNA templates. We then performed PET studies on individuals in the pedigree with a homozygous PLA2G6 mutation, and investigated the enzyme activity level of the mutation.
  
  
  RESULTS
  A homozygous missense mutation, c.G991T (p.D331Y), was identified in an autosomal recessive case. A younger sister of the p.D331Y-carrying patient was also homozygous for the mutation, but with no extrapyramidal symptoms. A PET study showed a substantial reduction in dopamine transporter (DAT) binding in the p.D331Y patient, and a slight reduction in DAT binding in his sister. In vitro, we experimentally demonstrate that the D331Y mutation caused an approximately 70%reduction in enzyme activity.
  
  
  CONCLUSIONS
  We have confirmed that the PLA2G6 gene allocated PARK14 locus and is associated with AREP.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, People's Republic of China.
authors.forename: C-h
authors.initials: CH
authors.lastname: Shi
authors.forename: B-s
authors.initials: BS
authors.lastname: Tang
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: Z-y
authors.initials: ZY
authors.lastname: Lv
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: L-z
authors.initials: LZ
authors.lastname: Luo
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: X-x
authors.initials: XX
authors.lastname: Yan
authors.forename: Q
authors.initials: Q
authors.lastname: Pan
authors.forename: K
authors.initials: K
authors.lastname: Xia
authors.forename: J-f
authors.initials: JF
authors.lastname: Guo
mesh_terms: D000328:Adult; D000818:Animals; D044466:Asian People / Q000235:genetics; D002461:Cell Line, Transformed; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000235:genetics*; D010767:Phosphorylcholine / Q000494:pharmacology; D010879:Piperazines; D049268:Positron-Emission Tomography / Q000379:methods; D011725:Pyridines; D012702:Serotonin Antagonists; D014162:Transfection / Q000379:methods
chemical_list: D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; C485184:enhanced green fluorescent protein; D010767:Phosphorylcholine; D049452:Green Fluorescent Proteins; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human