Mutation analyses in amyotrophic lateral sclerosis/parkinsonism–dementia complex of the Kii peninsula, Japan
Mutation analyses in amyotrophic lateral sclerosis/parkinsonism–dementia complex of the Kii peninsula, Japan
复制标题
日本纪伊半岛肌萎缩侧索硬化症/帕金森病-痴呆症复合体的突变分析
作者：
H. Tomiyama;Y. Kokubo;R. Sasaki;Yuanzhe Li;Yoko Imamichi;M. Funayama;Y. Mizuno;N. Hattori;S. Kuzuhara
为了阐明日本纪伊半岛肌萎缩侧索硬化症 (ALS)/帕金森病-痴呆症 (PDC) (Kii ALS/PDC) 的遗传背景，我们对三名病理诊断为 Kii ALS/PDC 的患者进行了扩展突变分析。对 19 个基因进行了直接测序分析，包括 ALS/额颞叶变性 (FTLD) 相关基因 (SOD2、SOD3、ALS2/alsin、SMN1、PGRN、ANG、VEGF、VCP、VAPB、DCTN1、CHMP2B 和 TARDBP 或 TDP-43)、tau 蛋白病相关基因 (GSK3β) 和帕金森病相关基因（α-突触核蛋白、LRRK2、parkin、DJ-1、PINK1 和 ATP13A2）。在 MAPT、α-突触核蛋白、TDP-43（或 TARDBP）、GSK3β 和 Parkin 筛选中进行基因剂量分析。我们没有发现这19个基因发生突变。我们发现所有三名患者都有一个纯合非同义 SNP (ALS2/alsin V368M)。 MAPT、α-突触核蛋白、TDP-43、GSK3β 和 Parkin 的基因剂量正常。目前的研究结果，加上之前对 MAPT 和 SOD1 突变的阴性研究，进一步阐明了所有外显子、外显子-内含子边界、或已报道的与 ALS、FTLD、帕金森病、突触核蛋白病、TDP-43 蛋白病和 tau 蛋白病相关的主要致病或易感基因的一些重排中缺乏致病突变。然而，家族聚集和缺乏任何环境因素表明 Kii ALS/PDC 是由其他尚未确定的遗传因素引起的。 © 2008 运动障碍协会
To clarify the genetic background of amyotrophic lateral sclerosis (ALS)/parkinsonism–dementia complex (PDC) of the Kii peninsula, Japan (Kii ALS/PDC), we performed extended mutation analyses of three patients with pathologically diagnosed Kii ALS/PDC. Direct sequencing analyses were performed in 19 genes, including ALS/frontotemporal lobar degeneration (FTLD)‐related genes (SOD2, SOD3, ALS2/alsin, SMN1, PGRN, ANG, VEGF, VCP, VAPB, DCTN1, CHMP2B, and TARDBP or TDP‐43), tauopathy‐related gene (GSK3β), and parkinsonism‐related genes (alpha‐synuclein, LRRK2, parkin, DJ‐1, PINK1, and ATP13A2). Gene dosage analyses were conducted in screening of MAPT, alpha‐synuclein, TDP‐43 (or TARDBP), GSK3β, and parkin. We found no mutation in the 19 genes. We found a homozygous nonsynonymous SNP (ALS2/alsin V368M) shared by all the three patients. Gene dosage was normal in MAPT, alpha‐synuclein, TDP‐43, GSK3β, and parkin. The present findings, together with a previous negative study on MAPT and SOD1 mutation, further elucidated the lack of causative mutations in all exons, exon–intron boundaries, or some rearrangements of the reported major causative or susceptible genes related to ALS, FTLD, parkinsonism, synucleinopathy, TDP‐43 proteinopathy, and tauopathy. However, the familial aggregation and lack of any environment factors suggest that Kii ALS/PDC is caused by other yet unidentified genetic factors. © 2008 Movement Disorder Society
DOI：
10.1073/pnas.0505149102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Hermosura, MC;Nayakanti, H;Garruto, RM
通讯作者：
Garruto, RM