Identification of the gene causing mucolipidosis type IV

Nat Genet. 2000 Sep;26(1):118-23. doi: 10.1038/79095.


Mucolipidosis type IV (MLIV) is an autosomal recessive, neurodegenerative, lysosomal storage disorder characterized by psychomotor retardation and ophthalmological abnormalities including corneal opacities, retinal degeneration and strabismus. Most patients reach a maximal developmental level of 12?15 months. The disease was classified as a mucolipidosis following observations by electron microscopy indicating the lysosomal storage of lipids together with water-soluble, granulated substances. Over 80% of the MLIV patients diagnosed are Ashkenazi Jews, including severely affected and mildly affected patients. The gene causing MLIV was previously mapped to human chromosome 19p13.2-13.3 in a region of approximately 1 cM (ref. 7). Haplotype analysis in the MLIV gene region of over 70 MLIV Ashkenazi chromosomes indicated the existence of two founder chromosomes among 95% of the Ashkenazi MLIV families: a major haplotype in 72% and a minor haplotype in 23% of the MLIV chromosomes (ref. 7, and G.B., unpublished data). The remaining 5% are distinct haplotypes found only in single patients. The basic metabolic defect causing the lysosomal storage in MLIV has not yet been identified. Thus, positional cloning was an alternative to identify the MLIV gene. We report here the identification of a new gene in this human chromosomal region in which MLIV-specific mutations were identified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Chromosome Mapping
  • Chromosomes, Human, Pair 19
  • Cloning, Molecular
  • CpG Islands
  • DNA Mutational Analysis
  • Exons
  • Expressed Sequence Tags
  • Female
  • Gene Deletion
  • Genes, Recessive
  • Genetic Markers
  • Haplotypes
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Models, Genetic
  • Molecular Sequence Data
  • Mucolipidoses / genetics*
  • Mutation*
  • Pedigree
  • Polymorphism, Genetic
  • RNA Splicing
  • RNA, Messenger / metabolism
  • Restriction Mapping
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • TRPM Cation Channels
  • Transient Receptor Potential Channels


  • Genetic Markers
  • MCOLN1 protein, human
  • Membrane Proteins
  • RNA, Messenger
  • TRPM Cation Channels
  • Transient Receptor Potential Channels