| Mucopolysaccharidosis type VII: characterization of mutations and molecular heterogeneity. | |
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MedLine Citation:
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PMID: 1702266 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We identified two different exonic point mutations causing beta-glucuronidase (beta G1) deficiency in two Japanese patients with mucopolysaccharidosis type VII (MPSVII). Enzyme assay of lysates of the lymphocytes and cultured fibroblasts showed little residual activity. The beta G1-specific mRNA levels were normal, as determined by northern blot analysis. Mutated cDNA clones, including the entire coding sequence, were isolated using the polymerase chain reaction (PCR) products derived from beta G1-deficient fibroblasts. Sequence analysis of the full-length mutated cDNAs showed C----T transitions, which resulted in a single Ala619----Val change (case 1, a 24-year-old male) and a Arg382----Cys change (case 2, a 7-year-old female). The former change was revealed by a loss of the cleavage site for the Fnu4HI in the mutated cDNA. On the basis of the loss of Fnu4HI restriction site, the patient (case 1) was a homozygote with this mutation. The mutational change in patient 2 was confirmed by direct sequencing and by demonstrating heterozygosity for the mutation in her parents. The Ala619----Val and Arg382----Cys mutations each disrupt a different domain which is highly conserved among human, rat, and Escherichia coli beta G1s. Each of these two amino acid changes reduced the beta G1 activity of the corresponding mutant beta G1 expressed following transfection of COS cells with expression vectors harboring the mutated cDNAs. |
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Authors:
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S Tomatsu; S Fukuda; K Sukegawa; Y Ikedo; S Yamada; Y Yamada; T Sasaki; H Okamoto; T Kuwahara; S Yamaguchi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American journal of human genetics Volume: 48 ISSN: 0002-9297 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 1991 Jan |
Date Detail:
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Created Date: 1991-02-05 Completed Date: 1991-02-05 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 89-96 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Gifu University School of Medicine, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Base Sequence Blotting, Northern Cells, Cultured Child DNA / genetics Female Fibroblasts / enzymology Genetic Variation* Glucuronidase / deficiency*, genetics Humans Lymphocytes / enzymology Male Molecular Sequence Data Mucopolysaccharidoses / genetics* Mutation* Polymerase Chain Reaction RNA / genetics Transfection |
| Chemical | |
Reg. No./Substance:
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63231-63-0/RNA; 9007-49-2/DNA; EC 3.2.1.31/Glucuronidase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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