Information de reference pour ce titreAccession Number: | 01445366-201001000-00020.
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Author: | Pohl, Sandra 1; Encarnacao, Marisa 1; Castrichini, Monica 1; Muller-Loennies, Sven 2; Muschol, Nicole 1; Braulke, Thomas 1
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Institution: | (1)Department of Biochemistry, Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (2)Division of Medical and Biochemical Microbiology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany Department of Biochemistry, Children's Hospital, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Building N27, 20246 Hamburg, Germany.
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Title: | |
Source: | American Journal Of Medical Genetics -A. 152A(1):124-132, January 2010.
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Abstract: | : Mucolipidosis type III gamma (MLIII, pseudo-Hurler polydystrophy) is a rare autosomal recessive disorder where the activity of the multimeric GlcNAc-1-phosphotransferase is reduced and formation of the mannose 6-phosphate (M6P) recognition marker on lysosomal enzymes is impaired. In this disease, the targeting of lysosomal enzymes is affected resulting in their hypersecretion, and an intracellular deficiency of multiple hydrolases. We report the biochemical and molecular diagnosis of MLIII in three siblings, aged 17, 15, and 14 years, who presented with joint pain and progressive joint stiffness. In addition to missorting of newly synthesized lysosomal protease cathepsin D, there were low levels of M6P-containing proteins in cell extracts and media of cultured fibroblasts of the Patients. Direct sequencing identified a novel homozygous mutation in intron 7, IVS7-10G>A, of the GNPTG gene, which encodes the [gamma]-subunit of the GlcNAc-1-phosphotransferase. This mutation created a cryptic 3'-splice site resulting in a frameshift and premature translational termination (p.V176GfsX18). The GNPTG mRNA levels were markedly reduced in Patients' fibroblasts indicating that the intronic mutation mediates mRNA decay, which was confirmed by absence of the [gamma]-subunit protein. These data contribute to an efficient diagnostic strategy to identify Patients with MLIII gamma and characterize their biochemical defect in fibroblasts. (C) 2009 Wiley-Liss, Inc.
Copyright (C) 2010 John Wiley & Sons, Inc.
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Author Keywords: | mucolipidosis III; GNPTG; mannose 6-phosphate; lysosomal enzymes; splicing mutation; intron retention.
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Language: | English.
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Document Type: | Research Articles.
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Journal Subset: | Life & Biomedical Sciences. Science.
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ISSN: | 1552-4825
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DOI Number: | https://dx.doi.org/10.1002/ajmg....- ouverture dans une nouvelle fenêtre
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