Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.
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.
Sun
M
M
Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Goldin
E
E
Stahl
S
S
Falardeau
J L
JL
Kennedy
J C
JC
Acierno
J S
JS
Bove
C
C
Kaneski
C R
CR
Nagle
J
J
Bromley
M C
MC
Colman
M
M
Schiffmann
R
R
Slaugenhaupt
S A
SA
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
C416674:MCOLN1 protein, human; D008565:Membrane Proteins; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels