{"title":"溶酶体贮积病的分子异质性。α -聚焦酶和n -乙酰- β - d -己糖氨酸酶缺乏变异体。","authors":"G Dawson, K Johnson, N R McCabe, L W Hancock","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>The availability of specific antibodies and cDNA probes for lysosomal hydrolases has revealed unexpected heterogeneity among the human inherited lysosomal storage diseases. Using alpha-fucosidase and N-acetyl-beta-D-hexosaminidase deficiency variants as examples, it has been determined that a lysosomal hydrolase deficiency can result from DNA deletion mutations, failure to synthesize mRNA because of defective splicing, posttranslational defects in assembly, and synthesis of a precursor enzyme that is prematurely proteolytically degraded through lack of a protective protein. In some cases (fucosidosis), the different genotypes cannot be distinguished phenotypically, whereas in others (beta-hexosaminidoses) the phenotypes can range from infantile neurodegeneration through juvenile motor neuron disease to adult neurodysfunction. Biochemical studies on both diseases have revealed several distinct genotypes. We show that some forms of fucosidosis result from unstable enzyme that can be stabilized by protease inhibitors, whereas partial beta-hexosaminidase deficiencies cannot be corrected by these protease inhibitors.</p>","PeriodicalId":77753,"journal":{"name":"Neurochemical pathology","volume":"8 3","pages":"203-17"},"PeriodicalIF":0.0000,"publicationDate":"1988-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Molecular heterogeneity in lysosomal storage diseases. Alpha-fucosidase and N-acetyl-beta-D-hexosaminidase deficiency variants.\",\"authors\":\"G Dawson, K Johnson, N R McCabe, L W Hancock\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The availability of specific antibodies and cDNA probes for lysosomal hydrolases has revealed unexpected heterogeneity among the human inherited lysosomal storage diseases. Using alpha-fucosidase and N-acetyl-beta-D-hexosaminidase deficiency variants as examples, it has been determined that a lysosomal hydrolase deficiency can result from DNA deletion mutations, failure to synthesize mRNA because of defective splicing, posttranslational defects in assembly, and synthesis of a precursor enzyme that is prematurely proteolytically degraded through lack of a protective protein. In some cases (fucosidosis), the different genotypes cannot be distinguished phenotypically, whereas in others (beta-hexosaminidoses) the phenotypes can range from infantile neurodegeneration through juvenile motor neuron disease to adult neurodysfunction. Biochemical studies on both diseases have revealed several distinct genotypes. We show that some forms of fucosidosis result from unstable enzyme that can be stabilized by protease inhibitors, whereas partial beta-hexosaminidase deficiencies cannot be corrected by these protease inhibitors.</p>\",\"PeriodicalId\":77753,\"journal\":{\"name\":\"Neurochemical pathology\",\"volume\":\"8 3\",\"pages\":\"203-17\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1988-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurochemical pathology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical pathology","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
溶酶体水解酶特异性抗体和cDNA探针的可用性揭示了人类遗传性溶酶体贮积病之间意想不到的异质性。以α -聚焦酶和n -乙酰- β - d -己糖氨酸酶缺乏症变体为例,已经确定溶酶体水解酶缺乏症可由DNA缺失突变、剪接缺陷导致mRNA合成失败、翻译后组装缺陷以及由于缺乏保护蛋白而过早蛋白水解降解的前体酶合成引起。在某些情况下(焦点病),不同的基因型不能在表型上区分,而在其他情况下(β -己糖氨基醇病),表型可以从婴儿神经退行性变到青少年运动神经元疾病到成人神经功能障碍。对这两种疾病的生化研究揭示了几种不同的基因型。我们表明,某些形式的聚焦病是由蛋白酶抑制剂稳定的不稳定酶引起的,而部分β -己糖氨酸酶缺乏不能通过这些蛋白酶抑制剂纠正。
Molecular heterogeneity in lysosomal storage diseases. Alpha-fucosidase and N-acetyl-beta-D-hexosaminidase deficiency variants.
The availability of specific antibodies and cDNA probes for lysosomal hydrolases has revealed unexpected heterogeneity among the human inherited lysosomal storage diseases. Using alpha-fucosidase and N-acetyl-beta-D-hexosaminidase deficiency variants as examples, it has been determined that a lysosomal hydrolase deficiency can result from DNA deletion mutations, failure to synthesize mRNA because of defective splicing, posttranslational defects in assembly, and synthesis of a precursor enzyme that is prematurely proteolytically degraded through lack of a protective protein. In some cases (fucosidosis), the different genotypes cannot be distinguished phenotypically, whereas in others (beta-hexosaminidoses) the phenotypes can range from infantile neurodegeneration through juvenile motor neuron disease to adult neurodysfunction. Biochemical studies on both diseases have revealed several distinct genotypes. We show that some forms of fucosidosis result from unstable enzyme that can be stabilized by protease inhibitors, whereas partial beta-hexosaminidase deficiencies cannot be corrected by these protease inhibitors.