title: Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.
abstract: Mucolipidosis type IV (MLIV) is a developmental neurodegenerative disorder characterized by severe neurologic and ophthalmologic abnormalities. The MLIV gene, ML4 (MCOLN1), has recently been localized to chromosome 19p13.2-13.3 by genetic linkage. Here we report the cloning of a novel transient receptor potential cation channel gene and show that this gene is mutated in patients with the disorder. ML4 encodes a protein, which we propose to call mucolipin, which has six predicted transmembrane domains and is a member of the polycystin II subfamily of the Drosophila transient receptor potential gene family. The role of a potential receptor-stimulated cation channel defect in the pathogenesis of mucolipidosis IV is discussed.
authors.affiliation: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sun
authors.forename: E
authors.initials: E
authors.lastname: Goldin
authors.forename: S
authors.initials: S
authors.lastname: Stahl
authors.forename: J L
authors.initials: JL
authors.lastname: Falardeau
authors.forename: J C
authors.initials: JC
authors.lastname: Kennedy
authors.forename: J S
authors.initials: JS
authors.lastname: Acierno
authors.forename: C
authors.initials: C
authors.lastname: Bove
authors.forename: C R
authors.initials: CR
authors.lastname: Kaneski
authors.forename: J
authors.initials: J
authors.lastname: Nagle
authors.forename: M C
authors.initials: MC
authors.lastname: Bromley
authors.forename: M
authors.initials: M
authors.lastname: Colman
authors.forename: R
authors.initials: R
authors.lastname: Schiffmann
authors.forename: S A
authors.initials: SA
authors.lastname: Slaugenhaupt
mesh_terms: D000595:Amino Acid Sequence; D002888:Chromosomes, Human, Pair 19; D020224:Expressed Sequence Tags; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009081:Mucolipidoses / Q000235:genetics*; D009154:Mutation; D020161:Physical Chromosome Mapping; D016415:Sequence Alignment; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels
chemical_list: C416674:MCOLN1 protein, human; D008565:Membrane Proteins; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels