PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort
PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort
复制标题
中国常染色体隐性早发性帕金森病的 PLA2G6 基因突变
DOI：
10.1212/wnl.0b013e318221acd3
复制
发表时间：
2011-07-01
期刊：
影响因子：
9.9
通讯作者：
Guo, J. -f.
中科院分区：
文献类型：
--
作者：
Shi, C. -h.;Tang, B. -s.;Guo, J. -f.
目的：复杂性帕金森综合征患者存在PLA 2G 6基因PARK 14位点突变。为了评估PLA 2G 6基因突变的患病率和相关表型，我们在一组常染色体隐性早发性帕金森综合征（AREP）患者中筛查了PLA 2G 6突变。方法：我们选择了12个AREP家系，其中Parkin，PINK 1，DJ-1，ATP 13 A2和FBXO 7基因突变已被排除。所有患者均来自中国大陆。从基因组DNA模板测序整个PLA 2G 6编码区和外显子-内含子边界。然后，我们对具有纯合PLA 2G 6突变的家系中的个体进行PET研究，并调查突变的酶活性水平。结果：在1例常染色体隐性遗传病例中发现一个纯合错义突变c.G991T（p.D331Y）。携带p.D331Y的患者的妹妹也是突变纯合子，但没有锥体外系症状。PET研究显示，p.D331Y患者的多巴胺转运蛋白（DAT）结合显著降低，其妹妹的DAT结合略有降低。在体外，我们实验证明D331 Y突变导致酶活性降低约70%。结论：PLA 2G 6基因位于PARK 14位点，与AREP相关。
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.