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GENATLAS PHENOTYPE
last update : 27-04-2011
Symbol ML4
Location 19p13.2
Name mucolipidosis IV
Other name(s) sialolipidosis
Corresponding gene MCOLN1
Other symbol(s) ML IV
Main clinical features
  • lysosomal storage disorder with an onset during the first year of life
  • characterized by corneal clouding, mental retardation, delayed motor milestones and achlorhydria, blindness, cognitive impairment, and psychomotor delays
  • associated with lysosomal inclusion bodies but no mucopolysaccharide excretion, skeletal changes or organomegaly
    • Genetic determination autosomal recessive
    Function/system disorder metabolism/lysosomal
    mental retardation
    neurology
    Type disease
    Gene product
    Name mucolipin 1, two founder mutations in Askenazi Jews, 1 splicing-1 deletion
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense     leading to enlarged lysosomes that are likely associated with abnormal sorting and trafficking of these and related organelles, and to disturbed Ca2+ signaling
    nonsense   abnormal protein/loss of function impairing lysosomal exocytosis
    Remark(s)
  • nonsense mutations, an 11bp insertion in exon 12, an in frame deletion (F408del)
  • impair the ability of MCOLN1 to permeate Fe(2+) at varying degrees, which correlate well with the disease severity, and impaired iron transport may contribute to both haematological and degenerative symptoms
  • chelatable zinc accumulation in large lysosomes and membranous vacuoles may contribute to the pathogenesis of the disease and progressive cell degeneration in MLIV patients (PMID: 20864526))
    • Genotype/Phenotype correlations mutation associated to disorder limited to the eyes and without the usual psychomotor deterioration (Dobrovolny 2007)