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[Corrections added on 20 July 2022 after first online publication: The funding information has been updated.]"],"award-info":[{"award-number":["12Q5920N to DS, 1842318 N and G0A3322N to FM. [Corrections added on 20 July 2022 after first online publication: The funding information has been updated.]"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The spondylodysplastic type of Ehlers\u2013Danlos syndrome (spEDS) is caused by genetic defects in the <jats:italic>B4GALT7<\/jats:italic> or <jats:italic>B3GALT6<\/jats:italic> genes both deranging the biosynthesis of the glycosaminoglycan linkage region of chondroitin\/dermatan sulfate and heparan sulfate proteoglycans. In this study, we have analyzed the linkage regions of urinary chondroitin sulfate proteoglycans of three siblings, diagnosed with spEDS and carrying biallelic pathogenic variants of the <jats:italic>B3GALT6<\/jats:italic> gene. Proteoglycans were digested with trypsin, glycopeptides enriched on anion\u2010exchange columns, depolymerized with chondroitinase ABC, and analyzed by nLC\u2010MS\/MS. In urine of the unaffected mother, the dominating glycopeptide of bikunin\/protein AMBP appeared as only one dominating (99.9%) peak with the canonical tetrasaccharide linkage region modification. In contrast, the samples of the three affected siblings contained two different glycopeptide peaks, corresponding to the canonical tetrasaccharide and to the non\u2010canonical trisaccharide linkage region modifications in individual ratios of 61\/38, 73\/27, and 59\/41. We propose that the relative distribution of glycosaminoglycan linkage regions of urinary bikunin glycopeptides may serve as a phenotypic biomarker in a diagnostic test but also as a biomarker to follow the effect of future therapies in affected individuals.<\/jats:p>","DOI":"10.1002\/jmd2.12311","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T06:14:14Z","timestamp":1656483254000},"page":"462-467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Glycosaminoglycan linkage region of urinary bikunin as a potentially useful biomarker for <scp>\u03b23GalT6<\/scp>\u2010deficient spondylodysplastic <scp>Ehlers\u2013Danlos<\/scp> syndrome"],"prefix":"10.1002","volume":"63","author":[{"given":"Mahnaz","family":"Nikpour","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Sahlgrenska Academy University of Gothenburg  Gothenburg 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