title: Mucolipidosis IV: report of a case with ocular restricted phenotype caused by leaky splice mutation.
abstract: OBJECTIVE
  To confirm and define a molecular basis for a case of mucolipidosis type IV (ML IV) with an extremely atypical phenotype pattern.
  
  
  METHODS
  Observational case report of a patient with ML IV with disease progression restricted to ocular symptoms.
  
  
  METHODS
  Complete ophthalmologic and neurologic examination. Ultrastructural examination of white blood cells, skin, conjunctiva, and corneal epithelium. The MCOLN1 gene was sequenced from cDNA and the proportion of splicing variants were assessed by quantitative allele-specific polymerase chain reaction.
  
  
  RESULTS
  Absence of any neurological abnormalities. Retinal pathologic features were the main cause of visual disability: low visual acuity and cloudy corneas since 2 years of age, progressive decrease in visual acuity since the age of 9 years. Ultrastructural examination showed storage lysosomes filled with either concentric membranes or lucent precipitate in corneal and conjunctive epithelia and in vascular endothelium. Cultured fibroblasts were free of any autofluorescence. Sequencing of the MCOLN1 gene identified compound heterozygosity for D362Y and A-->T transition leading to the creation of a novel donor splicing site and a 4-bp deletion from exon 13 at the mRNA level. Both normal and pathologic splice forms were detected in skin fibroblasts and leukocytes, with the normal form being more abundant.
  
  
  CONCLUSIONS
  The case of this patient with ML IV is unique and is characterized by a curious lack of generalized symptoms. In this patient, the disorder was limited to the eyes and appeared without the usual psychomotor deterioration. The resulting phenotype is the mildest seen to date.
authors.affiliation: Institute of Inherited Metabolic Diseases, First Medical Faculty and General Faculty Hospital, Charles University, Prague, Czech Republic.
authors.forename: Robert
authors.initials: R
authors.lastname: Dobrovolny
authors.forename: Petra
authors.initials: P
authors.lastname: Liskova
authors.forename: Jana
authors.initials: J
authors.lastname: Ledvinova
authors.forename: Helena
authors.initials: H
authors.lastname: Poupetova
authors.forename: Befekadu
authors.initials: B
authors.lastname: Asfaw
authors.forename: Martin
authors.initials: M
authors.lastname: Filipec
authors.forename: Katerina
authors.initials: K
authors.lastname: Jirsova
authors.forename: Josef
authors.initials: J
authors.lastname: Kraus
authors.forename: Milan
authors.initials: M
authors.lastname: Elleder
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D002648:Child; D003229:Conjunctival Diseases / Q000235:genetics / Q000473:pathology; D003316:Corneal Diseases / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004596:Electroretinography; D004847:Epithelial Cells / Q000648:ultrastructure; D019573:Epithelium, Corneal / Q000648:ultrastructure; D005260:Female; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D007962:Leukocytes / Q000648:ultrastructure; D008247:Lysosomes / Q000235:genetics / Q000648:ultrastructure; D009081:Mucolipidoses / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D012867:Skin / Q000648:ultrastructure; D050053:TRPM Cation Channels / Q000235:genetics*; D050051:Transient Receptor Potential Channels
chemical_list: C416674:MCOLN1 protein, human; D012333:RNA, Messenger; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels