{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:02:28Z","timestamp":1791356548062,"version":"4.3.1"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,7,6]]},"abstract":"<jats:p>\n                    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-\n                    <jats:italic>O<\/jats:italic>\n                    -sulfotransferase (C6ST-1) gene (\n                    <jats:italic>CHST3<\/jats:italic>\n                    ) changing an arginine into a glutamine (R304Q) in the well conserved 3\u2032-phosphoadenosine 5\u2032-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                    <jats:italic>N<\/jats:italic>\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 \u0394HexA-GalNAc(6S) and \u0394HexA(2S)-GalNAc(6S) were significantly reduced in the patient's cells and that \u0394HexA-GalNAc(4S,6S), undetectable in controls, was elevated. Analysis of the patient's urine shows marked undersulfation of CS, in particular reduction in 6-\n                    <jats:italic>O<\/jats:italic>\n                    -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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0400334101","type":"journal-article","created":{"date-parts":[[2004,6,23]],"date-time":"2004-06-23T20:20:10Z","timestamp":1088022010000},"page":"10155-10160","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":181,"title":["Loss of chondroitin 6-\n                    <i>O<\/i>\n                    -sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement"],"prefix":"10.1073","volume":"101","author":[{"given":"Holger","family":"Thiele","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Sakano","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Sugahara","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rajab","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"H\u00f6hne","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heide","family":"Ritter","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gundula","family":"Leschik","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Mundlos","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Institute of Biochemistry, Charit\u00e9 University Hospital, Humboldt University, Berlin 13353, Germany; Gene Mapping Center, Max Delbr\u00fcck Center for Molecular Medicine, Berlin 13092, Germany; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada, Kobe 658-8558, Japan; Genetic Unit, Directorate General of Health Affairs, Ministry of Health, 138 Muscat, Sultanate of Oman; and Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,6,23]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(00)00125-1"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01532-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01659331"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.50.31377"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2003.09.011"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.12.6615"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/2458"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/377110"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20606"},{"key":"e_1_3_2_11_2","first-page":"460","volume":"36","year":"1984","unstructured":"Lathrop, G. 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