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Vol. 96, Issue 15, 8562-8566, July 20, 1999

Genetics
 Mucolipidosis IV consists of one complementation group

Ehud Goldin*, Adele Cooney, Christine R. Kaneski, Roscoe O. Brady, and Raphael Schiffmann

Developmental Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20982-1260

Contributed by Roscoe O. Brady, May 24, 1999

Mucolipidosis IV (MLIV) is an autosomal recessive disorder of unknown etiology characterized by severe visual impairment and psychomotor retardation. Recently, there has been considerable interest in positional cloning of the MLIV gene. It is unknown whether MLIV is a genetically homogenous disorder. In this paper, we present experiments that determined whether the MLIV phenotype in fibroblasts could be corrected by fusing normal cells to MLIV cells and fusing fibroblasts from pairs of patients. All of our MLIV patients fulfilled several diagnostic criteria that we developed. In addition, we found high sensitivity to chloroquine in cultured fibroblasts from MLIV patients. We found that normal cells corrected the MLIV phenotype. Fusion products of normal and MLIV fibroblasts, but not MLIV fibroblasts themselves, were relatively protected against chloroquine selection. In addition, 74% of the normal-to-patient fusion products had reduced levels or total loss of MLIV characteristic autofluorescence. However, there was no complementation of the phenotype in fibroblast cultures from any of our MLIV patients, including those of non-Jewish ancestry. In fusion products of MLIV cultures from 24 patients, 90-100% of the cells remained autofluorescent. These results indicate that all of our known MLIV patients, regardless of ancestry or severity of the developmental defect, have a single mutated gene.

*   To whom reprint requests should be addressed at: Building 10, Room 3D04, National Institutes of Health, 10 Center Drive MSC1260, Bethesda, MD 20892-1260. e-mail: goldin{at}codon.nih.gov.

Copyright © 1999 by The National Academy of Sciences  0027-8424/99/968562-5$2.00/0
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