Mutation screening of PLA2G6 in Japanese patients with early onset dystonia-parkinsonism.
Mutation screening of PLA2G6 in Japanese patients with early onset dystonia-parkinsonism.
复制标题
日本早发性肌张力障碍-帕金森症患者的 PLA2G6 突变筛查。
DOI：
10.1007/s00702-016-1658-7
复制
发表时间：
2017
期刊：
影响因子：
3.3
通讯作者：
Hattori N.
中科院分区：
文献类型：
--
作者：
Yamashita C;Funayama M;Li Y;Yoshino H;Yamada H;Seino Y;Tomiyama H;Hattori N.
PLA 2G 6基因的隐性突变可引起婴儿神经轴索营养不良（INAD）和与脑铁积累相关的神经变性（NBIA），最近已被证明是PARK 14连锁的肌张力障碍-帕金森综合征的原因。为了研究PLA 2G 6突变的频率，包括帕金森综合征患者中由基因重排引起的突变，我们对109例日本帕金森综合征患者进行了直接测序并调查了该基因的拷贝数变异（CNVs）。直接测序发现了一个纯合突变（c.1495G>A; p.A499T），这可能是致病性的，已经登记为rs 141045127，和两个复合杂合突变，我们以前报道过。在我们的研究对象中未检测到PLA 2G 6的CNVs。我们的研究结果表明，CNV inPLA 2G 6是罕见的帕金森症，至少在日本的人口，相反，其频率在INAD的报告。需要在不同人群中进行进一步的大规模研究，以阐明是什么原因导致了INAD和肌张力障碍-帕金森综合征之间PLA 2G 6重排突变频率的差异。
A recessive mutation inPLA2G6, which is known to cause infantile neuroaxonal dystrophy (INAD) and neurodegeneration associated with brain iron accumulation (NBIA), has recently been shown to be responsible forPARK14-linked dystonia-parkinsonism. To study the frequency ofPLA2G6mutations, including those caused by gene rearrangement in patients with parkinsonism, we performed direct sequencing and investigated copy number variations (CNVs) of this gene in 109 Japanese patients with parkinsonism. Direct sequencing revealed a homozygous mutation (c.1495G>A; p.A499T), which is likely to be pathogenic and is already registered as rs141045127, and two compound-heterozygous mutations we have previously reported. No CNVs inPLA2G6were detected in our subjects. Our results suggest that CNV inPLA2G6is rare in parkinsonism, at least in the Japanese population, in contrast to the reports of its frequency in INAD. Further large studies in various populations are warranted to elucidate what causes the difference in frequencies ofPLA2G6rearrangement mutations between INAD and dystonia-parkinsonism.