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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
27
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pubmed:dateCreated |
2004-7-8
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pubmed:abstractText |
We studied two large consanguineous families from Oman with a distinct form of spondyloepiphyseal dysplasia (SED Omani type). By using a genome-wide linkage approach, we were able to map the underlying gene to a 4.5-centimorgan interval on chromosome 10q23. We sequenced candidate genes from the region and identified a missense mutation in the chondroitin 6-O-sulfotransferase (C6ST-1) gene (CHST3) changing an arginine into a glutamine (R304Q) in the well conserved 3'-phosphoadenosine 5'-phosphosulfate binding site. C6ST-1 catalyzes the modifying step of chondroitin sulfate (CS) synthesis by transferring sulfate to the C-6 position of the N-acetylgalactosamine of chondroitin. From the crystal structures of other sulfotransferases, it could be inferred that Arg-304 is essential for the structure of the cosubstrate binding site. We used recombinant C6ST-1 to show that the identified missense mutation completely abolishes C6ST-1 activity. Disaccharide composition analysis of CS chains by anion-exchange HPLC shows that both Delta HexA-GalNAc(6S) and Delta HexA(2S)-GalNAc(6S) were significantly reduced in the patient's cells and that Delta HexA-GalNAc(4S,6S), undetectable in controls, was elevated. Analysis of the patient's urine shows marked undersulfation of CS, in particular reduction in 6-O-sulfated disaccharide and an increase in the nonsulfated unit. Our results indicate that the mutation in CHST3 described here causes a specific but generalized defect of CS chain sulfation resulting in chondrodysplasia with major involvement of the spine.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-10222012,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-10742590,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-10781596,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-11017086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-11042448,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-11241838,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-11572857,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-11680681,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-11696535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-11821431,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-122434,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-12900795,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-14568616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-14568617,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-15098240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-1836753,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-230515,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-2669482,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-4270998,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-6585139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-8651312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-9395468,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-9597547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-9671738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-9714015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-9714738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-9771708,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15215498-9883891
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10155-60
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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pubmed:year |
2004
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pubmed:articleTitle |
Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement.
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pubmed:affiliation |
Institute of Medical Genetics, Charité University Hospital, Humboldt University, Berlin 13353, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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