{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T12:19:00Z","timestamp":1783772340185,"version":"3.55.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1993,2,1]]},"abstract":"Glycogen-storage disease type II (GSDII) is caused by the deficiency of lysosomal alpha-glucosidase (acid maltase). This paper reports on the analysis of the mutant alleles in an American black patient with an adult form of GSDII (GM1935). The lysosomal alpha-glucosidase precursor of this patient has abnormal molecular features: (i) the molecular mass is decreased, (ii) the phosphorylation is deficient and (iii) the proteolytic processing is impaired. Sequence analysis revealed four mutations leading to amino acid alterations: Asp-645-&gt;Glu, Val-816-&gt;Ile, Arg-854-&gt;Stop and Thr-927-&gt;Ile. By using allele-specific oligonucleotide hybridization on PCR-amplified cDNA we have demonstrated that the Arg-854-&gt;Stop mutation is located in one allele that is not expressed, and that the other allele contains the remaining three mutations. Each of the mutations was introduced in wild-type cDNA and expressed in COS cells to analyse the effect on biosynthesis, transport and phosphorylation of lysosomal alpha-glucosidase. The Val-816-&gt;Ile substitution appeared to have no significant effect in contrast with results [Martiniuk, Mehler, Bodkin, Tzall, Hirshhorn, Zhong and Hirschhorn (1991) DNA Cell Biol. 10, 681-687] and was therefore defined as a polymorphism. The Thr-927-&gt;Ile substitution deleting one of the seven glycosylation sites was found to be responsible for the decrease in molecular-mass, but not for the deficient proteolytic processing and phosphorylation. It did not cause the enzyme deficiency either. The third mutation leading to the Asp-645-&gt;Glu substitution was proven to account in full for the observed defects in transport, phosphorylation and proteolytic processing of the newly synthesized alpha-glucosidase precursor of the patient.<\/jats:p>","DOI":"10.1042\/bj2890687","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:30:37Z","timestamp":1439242237000},"page":"687-693","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The conservative substitution Asp-645\u2192Glu in lysosomal \u03b1-glucosidase affects transport and phosphorylation of the enzyme in an adult patient with glycogen-storage disease type II"],"prefix":"10.1042","volume":"289","author":[{"given":"M M P","family":"Hermans","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"de Graaff","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Kroos","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H A","family":"Wisselaar","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Willemsen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B A","family":"Oostra","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J J","family":"Reuser","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/289\/3\/687\/609263\/bj2890687.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/289\/3\/687\/609263\/bj2890687.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T18:12:56Z","timestamp":1637691176000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/289\/3\/687\/29903\/The-conservative-substitution-Asp-645-Glu-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,2,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1993,2,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj2890687","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,2,1]]}}}