H. Tomiyama and Y. Kokubo contributed equally to this work.
Mutation analyses in amyotrophic lateral sclerosis/parkinsonism–dementia complex of the Kii peninsula, Japan†
Article first published online: 29 AUG 2008
Copyright © 2008 Movement Disorder Society
Volume 23, Issue 16, pages 2344–2348, 15 December 2008
How to Cite
Tomiyama, H., Kokubo, Y., Sasaki, R., Li, Y., Imamichi, Y., Funayama, M., Mizuno, Y., Hattori, N. and Kuzuhara, S. (2008), Mutation analyses in amyotrophic lateral sclerosis/parkinsonism–dementia complex of the Kii peninsula, Japan. Mov. Disord., 23: 2344–2348. doi: 10.1002/mds.22262
Potential conflict of interest: None reported.
- Issue published online: 21 DEC 2008
- Article first published online: 29 AUG 2008
- Manuscript Accepted: 9 JUL 2008
- Manuscript Revised: 24 JUN 2008
- Manuscript Received: 4 FEB 2008
- Kii ALS/PDC;
- amyotrophic lateral sclerosis;
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