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Missense mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTA) in a patient with mucolipidosis II induces changes in the size and cellular distribution of GNPTG.
Hum Mutat 2006; 27(8):830-1HM

Abstract

Mucolipidosis type II (ML II; I-cell disease) and mucolipidosis III (ML III; pseudo Hurler polydystrophy) are autosomal recessively inherited disorders caused by a defective N-acetylglucosamine 1-phosphotransferase (phosphotransferase). The formation of mannose 6-phosphate markers in soluble lysosomal enzymes is impeded leading to their increased excretion into the serum, to cellular deficiency of multiple hydrolases, and lysosomal storage of non-digested material. Phosphotransferase deficiency is caused by mutations in GNPTA and GNPTG encoding phosphotransferase subunits. Here we report on an adolescent with progressive joint contractions and other signs of mucolipidosis II who survived to the age of 14 years. Impaired trafficking of lysosomal enzymes cathepsin D and -hexosaminidase in metabolically labeled fibroblasts was documented. Mutations in the GNPTG gene and alterations in the GNPTG mRNA level were not detected. A different electrophoretic mobility of the 97 kDa GNPTG dimer suggested posttranslational modification abrogating the compartmentalization of GNPTG in the Golgi apparatus. A nucleotide substitution in the GNPTA gene (c.3707A>T) was identified altering the predicted C-terminal transmembrane anchor of the phosphotransferase subunit. The data demonstrate that defective GNPTA not only impairs lysosomal enzyme targeting but also the availability of intact GNPTG required for phosphotransferase activity and assembly of subunits.

Authors+Show Affiliations

Department of Biochemistry, Children's Hospital, University Hospital Hamburg Eppendorf, Hamburg, Germany. stephan.tiede@uk-sh.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16835905

Citation

Tiede, Stephan, et al. "Missense Mutation in the N-acetylglucosamine-1-phosphotransferase Gene (GNPTA) in a Patient With Mucolipidosis II Induces Changes in the Size and Cellular Distribution of GNPTG." Human Mutation, vol. 27, no. 8, 2006, pp. 830-1.
Tiede S, Cantz M, Spranger J, et al. Missense mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTA) in a patient with mucolipidosis II induces changes in the size and cellular distribution of GNPTG. Hum Mutat. 2006;27(8):830-1.
Tiede, S., Cantz, M., Spranger, J., & Braulke, T. (2006). Missense mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTA) in a patient with mucolipidosis II induces changes in the size and cellular distribution of GNPTG. Human Mutation, 27(8), pp. 830-1.
Tiede S, et al. Missense Mutation in the N-acetylglucosamine-1-phosphotransferase Gene (GNPTA) in a Patient With Mucolipidosis II Induces Changes in the Size and Cellular Distribution of GNPTG. Hum Mutat. 2006;27(8):830-1. PubMed PMID: 16835905.
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TY - JOUR T1 - Missense mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTA) in a patient with mucolipidosis II induces changes in the size and cellular distribution of GNPTG. AU - Tiede,Stephan, AU - Cantz,Michael, AU - Spranger,Jürgen, AU - Braulke,Thomas, PY - 2006/7/13/pubmed PY - 2006/10/17/medline PY - 2006/7/13/entrez SP - 830 EP - 1 JF - Human mutation JO - Hum. Mutat. VL - 27 IS - 8 N2 - Mucolipidosis type II (ML II; I-cell disease) and mucolipidosis III (ML III; pseudo Hurler polydystrophy) are autosomal recessively inherited disorders caused by a defective N-acetylglucosamine 1-phosphotransferase (phosphotransferase). The formation of mannose 6-phosphate markers in soluble lysosomal enzymes is impeded leading to their increased excretion into the serum, to cellular deficiency of multiple hydrolases, and lysosomal storage of non-digested material. Phosphotransferase deficiency is caused by mutations in GNPTA and GNPTG encoding phosphotransferase subunits. Here we report on an adolescent with progressive joint contractions and other signs of mucolipidosis II who survived to the age of 14 years. Impaired trafficking of lysosomal enzymes cathepsin D and -hexosaminidase in metabolically labeled fibroblasts was documented. Mutations in the GNPTG gene and alterations in the GNPTG mRNA level were not detected. A different electrophoretic mobility of the 97 kDa GNPTG dimer suggested posttranslational modification abrogating the compartmentalization of GNPTG in the Golgi apparatus. A nucleotide substitution in the GNPTA gene (c.3707A>T) was identified altering the predicted C-terminal transmembrane anchor of the phosphotransferase subunit. The data demonstrate that defective GNPTA not only impairs lysosomal enzyme targeting but also the availability of intact GNPTG required for phosphotransferase activity and assembly of subunits. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/16835905/Missense_mutation_in_the_N-acetylglucosamine-1-phosphotransferase_gene_(GNPTA)_in_a_patient_with_mucolipidosis_II_induces_changes_in_the_size_and_cellular_distribution_of_GNPTG L2 - https://doi.org/10.1002/humu.9443 DB - PRIME DP - Unbound Medicine ER -