Mucolipidosis Type IV (MLIV; MIM 252650) is a lysosomal storage disorder that is characterized by severe neurological and ophthalmologic abnormalities. It is a progressive neurologic disease that usually presents during the first year of life with mental retardation, corneal opacities, and delayed motor milestones. The majority of MLIV children reaches a maximum development level of 15 months in language and motor function, and is eventually totally blind. It is a rare autosomal recessive disease and the majority of patients diagnosed to date are of Ashkenazi Jewish descent, however, non-Jewish patients have been reported. It is likely that many patients remain undiagnosed given the heterogeneous clinical spectrum of the disorder. While the oldest reported MLIV patient is currently 45 years of age, the majority of patients die at a young age. There is currently no treatment for this tragic disorder. Recently, the P.I. has mapped the MLIV gene to a 5.6 cM region on chromosome 19p13.2-13.3 by linkage analysis in 26 Ashkenazi Jewish families. In addition, they have determined that the ethnic bias seen in MLIV is due to a founder effect with two common founder haplotypes representing 95 percent of the chromosomes in the Ashkenazim. This haplotype analysis has provided a strategy for narrowing the location of the disease gene to a small stretch of genomic DNA. The current estimated size of the MLIV candidate region as determined by ancestral recombination events is 1.2 cM. The identification of new genetic markers along with the acquisition of additional MLIV patients should permit us to narrow this candidate region even further. They are now poised to identify the nature of the genetic defect in MLIV and characterize its mode of pathogenesis. The product of this work will be knowledge of the genetic cause of MLIV, the ability to screen for carriers of the disease, and a beginning to the exploration of the normal and abnormal function of the MLIV gene in both human and animal systems.
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