title: Acid-sensing ion channel (ASIC) 4 gene: physical mapping, genomic organisation, and evaluation as a candidate for paroxysmal dystonia.
abstract: Acid-sensing ion channels (ASICs) are protongated Na(+) channels. They have been implicated with synaptic transmission, pain perception as well as mechanoperception. ASIC4 is the most recent member of this gene family. It shows expression throughout the central nervous system with strongest expression in pituitary gland. ASIC4 is inactive by itself and its function is unknown. Mutations in ion channel subunits, which are homologues of ASICs lead to neurodegeneration in Caenorhabditis elegans. It has, therefore, been speculated that similar mutations in ASICs may be responsible for neurodegeneration in humans. Here, we show that ASIC4 maps to the long arm of chromosome 2 in close proximity to the locus for paroxysmal dystonic choreoathetosis (PDC), a movement disorder with unknown cause. Ion channel genes have been shown to cause several other paroxysmal neurologic disorders and are important candidate genes for PDC. We established the genomic organisation of the ASIC4 gene and screened a PDC pedigree for mutations in the coding region. Although we identified three polymorphisms in the Cterminal part of the ASIC4 protein, these were not present in each affected subject in the PDC kindred we analysed. Therefore, although the ASIC4 gene is physically mapped to the PDC locus, our data indicates that ASIC4 gene mutation is not the cause of PDC. It remains to be established if mutations in ASIC4 or other ASIC subunits may cause neurological disorders.
authors.affiliation: Department of Otolaryngology, Research Group of Sensory Physiology, University of Tübingen, Röntgenweg 11, D-72076 Tübingen, Germany. stefan.gruender@uni-tuebingen.de
authors.forename: S
authors.initials: S
authors.lastname: Gründer
authors.forename: H S
authors.initials: HS
authors.lastname: Geisler
authors.forename: S
authors.initials: S
authors.lastname: Rainier
authors.forename: J K
authors.initials: JK
authors.lastname: Fink
mesh_terms: D062565:Acid Sensing Ion Channels; D000595:Amino Acid Sequence; D001483:Base Sequence; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004421:Dystonia / Q000235:genetics; D005192:Family Health; D005260:Female; D005796:Genes / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D010375:Pedigree; D020161:Physical Chromosome Mapping; D011110:Polymorphism, Genetic; D015222:Sodium Channels / Q000235:genetics*
chemical_list: C112231:ASIC3 protein, human; C568270:ASIC4 protein, human; D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D004247:DNA