{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:09:17Z","timestamp":1773796157625,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020586","name":"storbyuniversitetet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["101107665"],"award-info":[{"award-number":["101107665"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006095","name":"Helse S\u00f8r-\u00d8st RHF","doi-asserted-by":"publisher","award":["2015095"],"award-info":[{"award-number":["2015095"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009252","name":"Science for Life Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009252","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Serine residues in the protein backbone of heavily glycosylated proteoglycans are bound to glycosaminoglycans through a tetrasaccharide linker. <jats:italic>UXS1<\/jats:italic> encodes UDP\u2010glucuronate decarboxylase 1, which catalyzes synthesis of UDP\u2010xylose, the donor of the first building block in the linker. Defects in other enzymes involved in formation of the tetrasaccharide linker cause so\u2010called linkeropathies, characterized by short stature, radio\u2010ulnar synostosis, decreased bone density, congenital contractures, dislocations, and more.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing was performed in a father and son who presented with a mild skeletal dysplasia, as well as the father's unaffected parents. Wild\u2010type and mutant <jats:italic>UXS1<\/jats:italic> were recombinantly expressed in <jats:italic>Escherichia coli<\/jats:italic> and purified. Enzyme activity was evaluated by LC\u2013MS\/MS. In\u00a0vivo effects were studied using HeparinRed assay and metabolomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The son had short long bones, normal epiphysis, and subtle metaphyseal changes especially in his legs. The likely pathogenic heterozygous variant NM_001253875.1(<jats:italic>UXS1<\/jats:italic>):c.557T&gt;A p.(Ile186Asn) detected in the son was de novo in the father. Purified Ile186Asn\u2010UXS1, in contrast to the wild\u2010type, was not able to convert UDP\u2010glucuronic acid to UDP\u2010xylose. Plasma glycosaminoglycan levels were decreased in both son and father.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first report linking <jats:italic>UXS1<\/jats:italic> to short\u2010limbed short stature in humans.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2472","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T09:57:31Z","timestamp":1718099851000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A monoallelic <scp><i>UXS1<\/i><\/scp> variant associated with short\u2010limbed short stature"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7903-9087","authenticated-orcid":false,"given":"Cecilie F.","family":"Rustad","sequence":"first","affiliation":[{"name":"Centre for Rare Disorders Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4860-4615","authenticated-orcid":false,"given":"Paul Hoff","family":"Backe","sequence":"additional","affiliation":[{"name":"Department of Microbiology Oslo University Hospital HF, Rikshospitalet  Oslo Norway"},{"name":"Department of Medical Biochemistry, Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0229-102X","authenticated-orcid":false,"given":"Chunsheng","family":"Jin","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility at Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Else","family":"Merckoll","sequence":"additional","affiliation":[{"name":"Unilabs Radiology Norway  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian","family":"Tveten","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Telemark Hospital Trust  Skien Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa Lucy","family":"Maciej\u2010Hulme","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Health Oslo Metropolitan University  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niclas","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Health Oslo Metropolitan University  Oslo Norway"},{"name":"Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9490-3141","authenticated-orcid":false,"given":"Trine","family":"Prescott","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Telemark Hospital Trust  Skien Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise Sand\u00e5s","family":"Sand","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berit","family":"Woldseth","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja Benedikte Prest\u00f8","family":"Elgst\u00f8en","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7697-857X","authenticated-orcid":false,"given":"\u00d8ystein L.","family":"Holla","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Telemark Hospital Trust  Skien Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/os.12382"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.02.035"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.386706"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2004.050799"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31686-6"},{"key":"e_1_2_10_7_1","volume-title":"Handbook of physical measurements","author":"Hall J. 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