{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T18:54:09Z","timestamp":1715799249001},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,6,2]],"date-time":"2005-06-02T00:00:00Z","timestamp":1117670400000},"content-version":"vor","delay-in-days":8372,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1982,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>I\u2010cell disease (mucolipidosis II) is a fatal childhood disorder affecting the expression of multiple lysosomal acid hydrolases. The disorder is characterized by clinical and biochemical heterogeneity which may reflect different mutants with a similar phenotype. Genetic complementation studies demonstrating genetic heterogeneity within this disorder are described utilizing cultured fibroblasts from 11 different patients. Fibroblasts from I\u2010cell disease (ICD) and from five different lysosomal storage diseases with single structural gene enzyme deficiencies were fused in different combinations, and fractions enriched for multinucleated heterokaryons were isolated and tested for acid hydrolase activity and electrophoretic mobility. In fusions of ICD fibroblasts and various single lysosomal enzyme\u2010deficient fibroblasts, the activity of the deficient enzyme and of the other ICD hydrolases were restored, demonstrating that ICD is not a lysosomal enzyme structural gene defect and that the ICD defect, and not just the single enzyme deficiency, is corrected. In fusions involving only I\u2010cell fibroblasts, at least two complementation groups were identified by the recovery of activities of all lysosomal enzymes tested in heterokaryons. These results demonstrate the existence of genetic heterogeneity within the disorder and suggest that different mutations can result in the I\u2010cell clinical and biochemical phenotype. The data support an altered post\u2010translational processing of lysosomal enzymes as the cause of ICD and suggest that at least two genes participate in this pathway.<\/jats:p>","DOI":"10.1002\/ajmg.1320120312","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T18:44:29Z","timestamp":1118515469000},"page":"343-353","source":"Crossref","is-referenced-by-count":17,"title":["Genetic heterogeneity of I\u2010cell disease is demonstrated by complementation of lysosomal enzyme processing mutants"],"prefix":"10.1002","volume":"12","author":[{"given":"T. B.","family":"Shows","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O. 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