A novel PLA2G6 gene mutation causes autosomal recessive early-onset parkinsonism with typical clinic

• 作 者: Ji-Feng GUO Qian PAN Kun XIA Bei-Sha TANG Chang-He SHI Lei WANG Zhan-Yun LV Jian WANG Lin-Zi LUO Lu SHEN Hong JIANG Xin-Xiang YAN
• 机 构: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China;Neurodeg
• 出 处: 中国神经科学学会第九届全国学术会议暨第五届会员代表大会
• 发表日期: 2011年1期
• 关键词: PLA2G6 PARK14 PET AREP

　　Objective Mutations in the PLA2G6 gene at the PARK14 locus have been reported in complicated parkinsonism patients.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 was with no extrapyramidal symptoms.A PET study showed a substantial reduction in dopamine transporter (DAT) binding in the p.D33 1Y 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.Conclusion We have confirmed that the PLA2G6 gene allocated PARK14 locus and is associated with AREP.