Studies on complementation of beta hexosaminidase deficiency in human GM2 gangliosidosis.
Complementation of beta hexosaminidase A (hex A) deficiency was obtained by Sendai virus-mediated somatic cell hybridization of cultured skin fibroblasts from two unrelated patients with Tay-Sachs disease (TSD) and one patient with Sandhoff-Jatzkewitz disease (SJD). The newly formed hex A was identified by its electrophoretic mobility in three different systems, heat lability, and reactivity with an antiserum against the unique antigenic determinant, alpha of hex A. The percentage of heterokaryons obtained by virus treatment of TSD and SJD fibroblast mixtures showed good correlation with the observed percentage of hex A activity. It is concluded that, in these two forms of GM2 gangliosidosis, beta hexosaminidase deficiency results from two different mutations. All of the current models of beta hexosaminidase structure are compatible with the observed complementation. No complementation was detected in 13 Sendai virus-induced fusions of cultured skin fibroblasts from seven unrelated patients with SJD. The enzyme deficiency in these patients may be due to very similar allelic mutations, not capable of undergoing complementation; or to different structural mutations, all coding for unstable beta hexosaminidase molecules.
D000118:Acetylglucosaminidase / Q000172:deficiency; D002459:Cell Fusion; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005733:Gangliosidoses / Q000201:enzymology / Q000235:genetics*; D005816:Genetic Complementation Test; D006596:Hexosaminidases / Q000172:deficiency*; D006801:Humans; D008064:Lipidoses / Q000235:genetics; D008297:Male; D009693:Nucleic Acid Hybridization; D012867:Skin / Q000201:enzymology
D006596:Hexosaminidases; D000118:Acetylglucosaminidase