{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:01:33Z","timestamp":1791356493920,"version":"4.3.1"},"reference-count":19,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2008,8,12]],"date-time":"2008-08-12T00:00:00Z","timestamp":1218499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2008,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spondyloepiphyseal dysplasia (SED), Omani type (OMIM 608637) is a recessively inherited skeletal dysplasia previously described in two distantly related families from the Republic of Oman. The phenotype consists of short stature, severe kyphoscoliosis, arthritic joints (elbows, wrists, knees), secondary large joint dislocations, rhizomelia, fusion of carpal bones and mild brachydactyly. Affected individuals were homozygous for a missense mutation, R304Q in <jats:italic>CHST3<\/jats:italic> that encodes the enzyme chondroitin 6\u2010<jats:italic>O<\/jats:italic>\u2010sulfotransferase\u20101 (C6ST\u20101). This enzyme mediates the sulfation of proteoglycans, particularly chondroitin sulfate (CS), in the extracellular matrix of cartilage. Here we describe the identification of a mutation (857T\u2009&gt;\u2009C predicting the substitution L286P) in <jats:italic>CHST3<\/jats:italic> in a Turkish family and extend the clinical phenotype of SED\u2010Omani type to include congenital joint dislocation, club feet, ventricular septal defect, deafness, metacarpal shortening and accessory carpal ossification centers. Fibroblasts and urine obtained from affected patients demonstrated negligible levels of 6\u2010<jats:italic>O<\/jats:italic>\u2010sulfated GalNAc residue in CS. Furthermore, the 6\u2010<jats:italic>O<\/jats:italic>\u2010sulfotransferase activity of cloned C6ST\u20101 into which the L286P mutation had been introduced was dramatically reduced, confirming the pathogenicity of this substitution. These results indicate that the clinical consequences of a deficiency of 6\u2010<jats:italic>O<\/jats:italic>\u2010sulfation in CS can be varied and that a clinical spectrum may exist similar to that seen in other skeletal dysplasias characterized by disorders of proteoglycan sulfation. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32482","type":"journal-article","created":{"date-parts":[[2008,8,12]],"date-time":"2008-08-12T18:27:16Z","timestamp":1218565636000},"page":"2376-2384","source":"Crossref","is-referenced-by-count":55,"title":["Spondyloepiphyseal dysplasia, Omani type: Further definition of the phenotype"],"prefix":"10.1002","volume":"146A","author":[{"given":"Mirjam H.H.","family":"van Roij","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Mizumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.B.","family":"Tan\u2010Sindhunata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Meijers\u2010Heijboer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.I.L.M.","family":"Verbeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Markie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Sugahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,8,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980806)78:5<468::AID-AJMG13>3.0.CO;2-D"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707082200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90281-X"},{"key":"e_1_2_7_5_1","first-page":"255","article-title":"Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate\u2010transporter gene (DTDST): Evidence for a phenotypic series involving three chondrodysplasias","volume":"58","author":"Hastbacka J","year":"1996","journal-title":"Am J Hum 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