title: TRPM7 is not associated with amyotrophic lateral sclerosis-parkinsonism dementia complex in the Kii peninsula of Japan.
abstract: Amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS/PDC) is a distinct neurodegenerative disorder characterized by ALS pathology with neurofibrillary tangles (NFTs) in the spinal cord and brain. Recent clinical studies have revealed a high incidence and a high familial occurrence of ALS/PDC in both Guam and the Kii peninsula of Japan, suggesting a strong genetic predisposition to this disorder. The T1482I variant (rs8042919) of TRPM7 gene which is suggested to play roles in regulating the cellular homeostasis of Ca(2+), Mg(2+), and trace metals, has recently been reported to be associated with Guamanian patients with ALS/PDC. To investigate whether TRPM7 is associated with Kii ALS/PDC, we conducted parametric linkage analyses of the TRPM7 locus in a large extended family with ALS/PDC. Linkage analysis did not reveal any evidence supporting the linkage to the TRPM7 locus. Resequencing of the entire coding region of TRPM7 did not reveal any pathogenic mutations in an affected individual in this family. The allele frequencies of the T1482I in affected individuals in this family or in those from other families are not significantly different from those in regional controls or those in HapMap-JPT samples. These results indicate that TRPM7 is not associated with ALS/PDC in the Kii peninsula of Japan.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Kenju
authors.initials: K
authors.lastname: Hara
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kokubo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ishiura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Akinori
authors.initials: A
authors.lastname: Miyashita
authors.forename: Ryozo
authors.initials: R
authors.lastname: Kuwano
authors.forename: Ryogen
authors.initials: R
authors.lastname: Sasaki
authors.forename: Jun
authors.initials: J
authors.lastname: Goto
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kuzuhara
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15; D003704:Dementia / Q000453:epidemiology / Q000235:genetics*; D008040:Genetic Linkage; D006706:Homeostasis; D006801:Humans; D007564:Japan / Q000453:epidemiology; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels / Q000235:genetics*
chemical_list: D050053:TRPM Cation Channels; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human