Abstract
We report a missense mutation in an adult Japanese patient with acid alpha-glucosidase (GAA) deficiency. A TC to GT transition at nucleotides 1585–1586, was identified. This transition resulted in an amino acid substitution of Ser-529 to Val (S529V) in exon 11. We also have demonstrated that the S529V mutation abolishes the catalytic activity of the enzyme. Our data suggest that this mutation is the cause of the clinical manifestation known as adult-onset GAA deficiency. The missense mutation described here is a new mutation, and the first identified in Japanese patients with GAA deficiency.
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Deng WP, Nickoloff JA (1992) Site-directed mutagenesis of virtually any plasmid by eliminating a unique site. Anal Biochem 200:81–88
Engel AG, Gomez MR, Seybold ME, Lambert EH (1973) The spectrum and diagnosis of acid maltase deficiency. Neurology 23:95–106
Hermans MMP, Graaf E de, Kroos MA, Wisselaar HA, Oostra BA, Reuser AJJ (1991) Identification of a point mutation in the human lysosomal α-glucosidase gene causing infantile glycogenesis type II. Biochem Biophys Res Commun 179:919–926
Hermans MMP, Graaf E de, Kroos MA, Wisselaar HA, Willemsen R, Oostra BA, Reuser AJJ (1993a) The conservative substitution Asp-645→Glu in lysosomal α-glucosidase affects transport and phosphorylation of the enzyme in an adult patient with glycogen-storage disease type II. Biochem J 289:687–693
Hermans MM, Kroos MA, Graaff E de, Oostra BA, Reuser AJ (1993b) Two mutations affecting the transport and maturation of lysosomal alpha-glucosidase in an adult case of glycogen storage disease type II. Hum Mutat 2:268–273
Hermans MMP, Graaff E de, Kroos MA, Mohkamsing M, Eussen BJ, Joosse M, Willemsen R, Kleijer WJ, Oostra BA, Reuser AJJ (1994) The effect of a single base pair deletion (ΔT525) and a T1634T missense mutation (pro5451eu) on the expression of lysosomal α-glucosidase in patients with glycogen storage disease type II. Hum Mol Genet 3:2213–2218
Hers HG (1963) Alpha-glucosidase deficiency in generalized glycogen storage disease (Pompe's disease). Biochem J 86:11–16
Hoefsloot LH, Hoogeven-Westerveld M, Kress Ma, Beeumen J van, Reuse AJJ, Oostra BA (1988) Primary structure and processing of lysosomal alpha-glucosidase; homology with the intestinal sucrase-isomaltase complex. EMBO J 7:1697–1704
Hoefsloot LH, Ploeg AT van der, Kress MA, Hoogeveen-Westerveld M, Oostra BA, Reuser AJJ (1990) Adult and infantile glycogenesis type II in one family, explained by allelic diversity. Am J Hum Genet 46:45–52
Huie ML, Chen AS, Tsujino S, Shanske S, Dimauro S, Engel AG, Hirschhorn H (1994) Aberrant splicing in adult onset glycogen storage disease type II (GSD II): molecular identification of an IVS 1 (-13T→G) mutation in a majority of patients and a novel IVS10 (+1GT→CT) mutation. Hum Mol Genet 3:2231–2236
Martiniuk F, Hirschhorn R (1981) Characterization of neutral isozymes of human alpha-glucosidase. Biochim Biophys Acta 658: 248–261
Martiniuk F, Mehler M, Pellicer A, Tzall S, La Badie G, Hobart C, Ellenbogen A, Hirschhorn R (1986) Isolation of a cDNA for human acid a-glucosidase and detection of genetic heterogeneity for mRNA in three α-glucosidase-deficient patients. Proc Natl Acad Sci USA 83:9641–9644
Martiniuk F, Mehler M, Tzall S, Meredith G, Hirschhorn R (1990a) Sequence of cDNA and 5″-flanking region for human acid α-glucosidase, detection of an intron in the 5′ untranslated leader sequence, definition of 18-bp polymorphisms, and differences with previous cDNA and amino acid sequences. DNA Cell Biol 9:85–94
Martiniuk F, Mehler M, Tzall S, Meredith G, Hirschhorn R (1990b) Extensive genetic heterogeneity in patients with acid alpha-glucosidase deficiency as detected by abnormalities of DNA and mRNA. Am J Hum Genet 47:73–78
Martiniuk F, Bodkin M, Tzall S, Hirschhorn R (1990c) Identification of the base-pair substitution responsible for a human acid alpha-glucosidase allele with lower “affinity” for glycogen (GAA2) and transient gene expression in deficient cells. Am J Hum Genet 47:440–445
Martiniuk F, Mehler M, Bodkin M, Tzall S, Hirschhorn K, Zhong N, Hirschhorn R (1991) Identification of a missense mutation in an adult-onset patient with glycogenesis type II expressing only one allele. DNA Cell Biol 10: 681–687
Mehler M, Dimauro S (1977) Residual acid maltase activity in late onset acid maltase deficiency. Neurology 27:178–184
Pompe JC (1932) Over idiopatische hypertrophie van het hart. Ned Tijdschr Geneeskd 76:304–311
Reuser AJJ, Kroos M, Oude Elferink RPJ, Tager JM (1985) Defects in synthesis, phosphorylation, and maturation of acid alpha-glucosidase in glycogenesis type II. J Biol Chem 260: 8336–8341
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
Shieh JJ, Wang LY, Lin CY (1994) Point mutation in Pompe disease (in Chinese). J Inherit Metab Dis 17:145–148
Tager JM, Oude Elferink RPJ, Kroos MA, Hoogeveen-Westerveld M, Oostra BA, Reuser AJJ (1987) Alpha-glucosidase deficiency (Pompe's disease). Enzyme 38:280–285
Zhong M, Martiniuk F, Tzall S, Hirschhorn R (1991) Identification of a missense mutation in one allele of a patient with Pompe disease, and use of endonuclease digestion of PCR-amplified RNA to demonstrate lack of mRNA expression from the second allele. Am J Hum Genet 4:635–645
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Tsunoda, H., Ohshima, T., Tohyama, J. et al. Acid alpha-glucosidase deficiency: Identification and expression of a missense mutation (S529V) in a Japanese adult phenotype. Hum Genet 97, 496–499 (1996). https://doi.org/10.1007/BF02267074
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DOI: https://doi.org/10.1007/BF02267074