STUDIES ON COMPLEMENTATION OF BETA-HEXOSAMINIDASE DEFICIENCY IN HUMAN GM2 GANGLIOSIDOSIS

Abstract

Complementation of .beta. hexosaminidase A (hex A) deficiency was obtained by Sendai virus-mediated somatic cell hybridization of cultured skin fibroblasts from 2 unrelated patients with Tay-Sachs disease (TSD) and 1 patient with Sandhoff-Jatzkewitz disease (SJD). The newly formed hex A was identified by its electrophoretic mobility in 3 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. In these 2 forms of GM2 gangliosidosis, .beta. hexosaminidase deficiency apparently results from 2 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 7 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.