Evidence for a hybrid hexosaminidase isoenzyme in heterozygotes for Sandhoff disease.
Patients with Sandhoff disease have less than 5% of normal levels of serum or tissue hexosaminidase activity. They are thought to have a defect in the structural gene for the beta chain of hexosaminidase (HEX). Heterozygotes for Sandhoff disease have approximately 50% of the total serum HEX activity of normals and more than 75% of the HEX is heat-labile. In normals, only 55%--65% of serum HEX is heat-labile. Serum HEX separates into three forms on DEAE cellulose chromatography: HEX A, a tetramer of 2 alpha and 2 beta chains, and HEX I and B composed solely of beta chains. The DEAE chromatograms from normals and Sandhoff heterozygotes did not differ in the relative distribution of HEX activity between peaks. In normals, the HEX A peak was heat-labile (60 degrees C for 9 min), but HEX I and B were heat-stable. In Sandhoff heterozygotes, however, HEX I and B were only 50%--53% heat-stable. This suggests the heterozygotes synthesized a hybrid enzyme containing both mutant and wild-type beta chains for HEX. The mutant beta chain renders the isoenzyme less stable to heating.
D005260:Female; D006579:Heterozygote; D006596:Hexosaminidases / Q000097:blood / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000097:blood / Q000235:genetics*; D009154:Mutation; D011247:Pregnancy; D012497:Sandhoff Disease / Q000201:enzymology* / Q000235:genetics
D007527:Isoenzymes; D006596:Hexosaminidases