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Two mutations affecting the transport and maturation of lysosomal α‐glucosidase in an adult case of glycogen storage disease type II
Author(s) -
Hermans Monique M. P.,
Kroos Marian A.,
De Graaff Esther,
Oostra Ben A.,
Reuser Arnold J. J.
Publication year - 1993
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380020406
Subject(s) - glycogen storage disease type ii , biology , glycogen storage disease , exon , lysosomal storage disease , mutant , glycogen debranching enzyme , mutation , allele , point mutation , wild type , microbiology and biotechnology , transition (genetics) , enzyme , genetics , biochemistry , gene , glycogen synthase , glycogen , medicine , disease , enzyme replacement therapy
The autosomal recessive glycogen storage disease type II is associated with a deficiency of lysosomal α‐glucosidase (acid maltase). This paper reports on the mutations in the lysosomal α‐glucosidase alleles of an adult patient. A G‐1927 to A transition was discovered in exon 14 causing the substitution of Gly‐643 by Arg and a second C‐2173 to T transition in exon 15 resulting in the substitution of Arg‐725 by Trp. Each of the mutations was located in a different allele. The mutations were introduced in the wild‐type lysosomal α‐glucosidase cDNA and expressed in COS cells. Both mutations had a similar effect. The synthesis of the mutant enzyme precursors was not disturbed but the intracellular transport and maturation were impaired. As a result there was an overall deficiency of catalytic activity. © 1993 Wiley‐Liss, Inc.