| Mucopolysaccharidosis IVA: structural gene alterations identified by Southern blot analysis and identification of racial differences. | |
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MedLine Citation:
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PMID: 7705830 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ninety-six alleles (36 alleles of Japanese and 60 of Caucasian origin) from forty-eight patients with mucopolysaccharidosis IVA were investigated for structural gene alterations using Southern blot analysis. All patients had a previously demonstrated deficiency of N-acetyl-galactosamine-6-sulfate-sulfatase and exhibited a wide spectrum of clinical severity. Initially, using the full-length cDNA as a probe, five of 36 chromosomes from the Japanese patients revealed similar rearrangements with respect to DNA digested with BamHI, SacI, and XhoI. Subsequent analysis using seven genomic fragments, covering the entire gene, enhanced the detection of aberrant fragments produced by the above restriction enzymes. Conversely, the 60 chromosomes of Caucasian origin revealed no evidence of large structural rearrangements when analyzed by these methods. There was a statistically significant difference between the two populations (P < 0.01). A severely affected Japanese patient showed structural rearrangements on both chromosomes by means of BamHI blots. An 8.0-kb fragment and a highly polymorphic 7.0-kb to 11.0-kb fragment present in normal individuals disappeared and two aberrant fragments of 11.5 kb and 12.0 kb were observed. Three other Japanese patients also showed these two aberrant fragments, in addition to the normal fragment pattern, and were thus heterozygous for this rearrangement. Interpretation of Southern blots was difficult because of the complexity of polymorphic bands resulting from variable number of tandem repeat elements. However, by utilizing these aberrant fragments or polymorphic bands, carrier detection was effective, even in families with poorly characterized mutations. Hybridization with probe MG-A (5'-end genomic probe in intron 1) showed a 8.4-kb fragment in BamHI blots of one Japanese and one Caucasian patient; XhoI, SacI, and EcoRI blots were normal. Since this BamHI alteration was also observed in one normal control, it appears to be a rare nonpathological polymorphism. |
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Authors:
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S Tomatsu; S Fukuda; A Cooper; J E Wraith; A Uchiyama; T Hori; Y Nakashima; N Yamada; K Sukegawa; N Kondo |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Human genetics Volume: 95 ISSN: 0340-6717 ISO Abbreviation: Hum. Genet. Publication Date: 1995 Apr |
Date Detail:
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Created Date: 1995-05-11 Completed Date: 1995-05-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7613873 Medline TA: Hum Genet Country: GERMANY |
Other Details:
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Languages: eng Pagination: 376-81 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Gifu University School of Medicine, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Blotting, Southern Continental Population Groups DNA / analysis* DNA Probes Female Gene Rearrangement* Genes / genetics* Humans Japan Male Mucopolysaccharidosis IV / ethnology*, genetics* Pedigree Sulfatases / deficiency |
| Chemical | |
Reg. No./Substance:
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0/DNA Probes; 9007-49-2/DNA; EC 3.1.6.-/Sulfatases; EC 3.1.6.14/N-acetylglucosamine-6-sulfatase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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