Gaucher disease: genetic heterogeneity within and among the subtypes detected by immunoblotting.

摘要: The genetic heterogeneity of Gaucher disease subtypes and variants was investigated by immunoblotting fibroblast extracts. For these studies polyclonal monoclonal antibodies were raised to acid beta-glucosidase preparations containing a single N-terminal amino sequence that colinear with encoded the beta-Glc cDNAs. Three forms (Mr approximately equal 67,000, 64,000-61,000, 58,000) cross-reacting immunologic material (CRIM) observed in control individuals. Decreased amounts same CRIM detected most type 1 patients, but variable molecular weight several non-Jewish variants. One or two found neuronopathic (type 2 3) patients. amount severely decreased majority 3 patients; one American black patient negative. With this exception, form cell-free culture media from all normal fibroblasts had an Mr 2,000 greater than highest respective intracellular molecular-weight form. All intra- extracellular reduced after deglycosylation N-Glycanase. In addition, radioactivity [3H]Br-conduritol B epoxide, specific covalent inhibitor beta-Glc, localized on immunoblots. These results indicate result mutations alter stability and/or processing beta-Glc. Furthermore, patterns within among cause diagnostic usefulness be restricted those families which phenotype has been well established.