Identification of the gene causing mucolipidosis type IV
- PMID: 10973263
- DOI: 10.1038/79095
Identification of the gene causing mucolipidosis type IV
Abstract
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MLIV families: a major haplotype in 72% and a minor haplotype in 23% of the MLIV chromosomes (ref. 7, and G.B., unpublished data).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.
Similar articles
-
Mucolipidosis type IV.Mol Genet Metab. 2001 Jul;73(3):197-203. doi: 10.1006/mgme.2001.3195. Mol Genet Metab. 2001. PMID: 11461186 Review.
-
A physical and transcript map of the MCOLN1 gene region on human chromosome 19p13.3-p13.2.Genomics. 2001 Apr 15;73(2):203-10. doi: 10.1006/geno.2001.6526. Genomics. 2001. PMID: 11318610
-
Cloning of the gene encoding a novel integral membrane protein, mucolipidin-and identification of the two major founder mutations causing mucolipidosis type IV.Am J Hum Genet. 2000 Nov;67(5):1110-20. doi: 10.1016/S0002-9297(07)62941-3. Epub 2000 Sep 29. Am J Hum Genet. 2000. PMID: 11013137 Free PMC article.
-
Mucolipidosis type IV: the origin of the disease in the Ashkenazi Jewish population.Eur J Hum Genet. 1999 May-Jun;7(4):496-8. doi: 10.1038/sj.ejhg.5200277. Eur J Hum Genet. 1999. PMID: 10352940
-
The molecular basis of mucolipidosis type IV.Curr Mol Med. 2002 Aug;2(5):445-50. doi: 10.2174/1566524023362276. Curr Mol Med. 2002. PMID: 12125810 Review.
Cited by
-
A blood-brain barrier-penetrant AAV gene therapy improves neurological function in symptomatic mucolipidosis IV mice.Mol Ther Methods Clin Dev. 2024 May 21;32(2):101269. doi: 10.1016/j.omtm.2024.101269. eCollection 2024 Jun 13. Mol Ther Methods Clin Dev. 2024. PMID: 38934011 Free PMC article.
-
Drosophila TRP channels and animal behavior.Life Sci. 2013 Mar 19;92(8-9):394-403. doi: 10.1016/j.lfs.2012.07.029. Epub 2012 Aug 1. Life Sci. 2013. PMID: 22877650 Free PMC article. Review.
-
Caenorhabditis elegans functional orthologue of human protein h-mucolipin-1 is required for lysosome biogenesis.Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4483-8. doi: 10.1073/pnas.0400709101. Epub 2004 Mar 15. Proc Natl Acad Sci U S A. 2004. PMID: 15070744 Free PMC article.
-
Cross-sectional Observations on the Natural History of Mucolipidosis Type IV.Neurol Genet. 2022 Mar 10;8(2):e662. doi: 10.1212/NXG.0000000000000662. eCollection 2022 Apr. Neurol Genet. 2022. PMID: 35425852 Free PMC article.
-
A Structural Overview of TRPML1 and the TRPML Family.Handb Exp Pharmacol. 2023;278:181-198. doi: 10.1007/164_2022_602. Handb Exp Pharmacol. 2023. PMID: 35879577
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
