title: Four novel rare mutations of PLA2G6 in Chinese population with Parkinson's disease.
abstract: BACKGROUND
  Mutations in the phospholipase A2 Group 6 (PLA2G6) gene have been identified in autosomal recessive neurodegenerative diseases classified as infantile neuroaxonal dystrophy and neurodegeneration with brain iron accumulation. Recently, PLA2G6 was also reported as the causative gene for early-onset PARK14-linked dystonia-parkinsonism.
  
  
  RESULTS
  To address whether PLA2G6 mutations are also an important cause of PD, we screened sequence variants of PLA2G6 in 250 PD patients and 550 controls in a Chinese Han populations. We identified four sequence changes: a coding synonymous c.1959T>A transition of exon13 in one patient, two missense mutations c.1966C>G in exon13 and c.2077C>G in exon14 in two different patients, which caused two amino acids change Leu656Val and Leu693Val respectively. We also found a frame-shift mutation P.His597fx69 in exon 12 in one patient. These four rare variants were not represented in 550 control individuals. Furthermore, we found that WT PLA2G6 enzyme hydrolyzed phospholipids while mutant PLA2G6 with P.His597fx69 frame-shift caused loss of enzyme activity, exhibiting less than 6% of the specific activity in phospholipase assays compared to that of WT PLA2G6. Mutant PLA2G6 with Leu656Val and Leu693Val decreased their activity by 45% and 35% in phospholipase assay respectively.
  
  
  CONCLUSIONS
  We identified four rare PLA2G6 mutations in 250 PD patients, enlarging the spectrum of PLA2G6 mutations in PD. Although PLA2G6 mutations account for only a small fraction of PD patients in Chinese populations, these mutations impair catalytic activity of their phospholipids-hydrolyzing function. These results indicate that PLA2G6 mutations maybe PD-causing in Chinese Han populations.
authors.affiliation: Department of Neurology, Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, 3 Qingchun East Road, Hangzhou, Zhejiang 310016, China.
authors.forename: Ya-Xing
authors.initials: YX
authors.lastname: Gui
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Xu
authors.lastname: Wen-Lv
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Liu
authors.forename: Jin-Jia
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Xing-Yue
authors.initials: XY
authors.lastname: Hu
mesh_terms: D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D054467:Phospholipases A2 / Q000235:genetics
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human; D054467:Phospholipases A2