title: Isolated ocular disease is associated with decreased mucolipin-1 channel conductance.
abstract: OBJECTIVE
  To evaluate a 15-year-old boy with MLIV (mucolipidosis type IV) and clinical abnormalities restricted to the eye who also had achlorhydria with elevated blood gastrin levels.
  
  
  METHODS
  In addition to a detailed neuro-ophthalmic and electrophysiological assessment, his mutant mucolipin-1 was experimentally expressed in liposomes and its channel properties studied in vitro.
  
  
  RESULTS
  The patient was a compound heterzygote for c.920delT and c.1615delG. Detailed neuro-ophthalmic examination including electroretinography showed him to have a typical retinal dystrophy predominantly affecting rod and bipolar cell function. In vitro expression of MCOLN1 in liposomes showed that the c.1615delG mutated channel had significantly reduced conductance compared with wild-type mucolipin-1, whereas the inhibitory effect of low pH and amiloride remained intact.
  
  
  CONCLUSIONS
  These findings suggest that reduced channel conductance is relatively well tolerated by the brain during development, whereas retinal cells and stomach parietal cells require normal protein function. MLIV should be considered in patients with retinal dystrophy of unknown cause and screened for using blood gastrin levels.
authors.affiliation: Molecular Neurogenetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ehud
authors.initials: E
authors.lastname: Goldin
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Caruso
authors.forename: William
authors.initials: W
authors.lastname: Benko
authors.forename: Christine R
authors.initials: CR
authors.lastname: Kaneski
authors.forename: Stephanie
authors.initials: S
authors.lastname: Stahl
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
mesh_terms: D000126:Achlorhydria / Q000150:complications; D000293:Adolescent; D004596:Electroretinography; D005755:Gastrins / Q000097:blood; D017353:Gene Deletion; D006147:Guanine; D006579:Heterozygote; D006801:Humans; D008297:Male; D009081:Mucolipidoses / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D009154:Mutation; D051245:Retinal Bipolar Cells; D012164:Retinal Diseases / Q000175:diagnosis* / Q000209:etiology* / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D013941:Thymine; D050051:Transient Receptor Potential Channels
chemical_list: D005755:Gastrins; C416674:MCOLN1 protein, human; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; D006147:Guanine; D013941:Thymine