{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:44:34Z","timestamp":1790325874776,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP180102630"],"award-info":[{"award-number":["DP180102630"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009578","name":"Mizutani Foundation for Glycoscience","doi-asserted-by":"publisher","award":["160151"],"award-info":[{"award-number":["160151"]}],"id":[{"id":"10.13039\/100009578","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["0090281"],"award-info":[{"award-number":["0090281"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We report the case of a consanguineous couple who lost four pregnancies associated with skeletal dysplasia. Radiological examination of one fetus was inconclusive. Parental exome sequencing showed that both parents were heterozygous for a novel missense variant, p.(Pro133Leu), in the SLC35D1 gene encoding a nucleotide sugar transporter. The affected fetus was homozygous for the variant. The radiological features were reviewed, and being similar, but atypical, the phenotype was classified as a \u2018Schneckenbecken-like dysplasia.\u2019 The effect of the missense change was assessed using protein modelling techniques and indicated alterations in the mouth of the solute channel. A detailed biochemical investigation of SLC35D1 transport function and that of the missense variant p.(Pro133Leu) revealed that SLC35D1 acts as a general UDP-sugar transporter and that the p.(Pro133Leu) mutation resulted in a significant decrease in transport activity. The reduced transport activity observed for p.(Pro133Leu) was contrasted with in vitro activity for SLC35D1 p.(Thr65Pro), the loss-of-function mutation was associated with Schneckenbecken dysplasia. The functional classification of SLC35D1 as a general nucleotide sugar transporter of the endoplasmic reticulum suggests an expanded role for this transporter beyond chondroitin sulfate biosynthesis to a variety of important glycosylation reactions occurring in the endoplasmic reticulum.<\/jats:p>","DOI":"10.1093\/hmg\/ddz200","type":"journal-article","created":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T15:11:12Z","timestamp":1565881872000},"page":"3543-3551","source":"Crossref","is-referenced-by-count":15,"title":["A hypomorphic allele of SLC35D1 results in Schneckenbecken-like dysplasia"],"prefix":"10.1093","volume":"28","author":[{"given":"Carsten","family":"Rautengarten","sequence":"first","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver W","family":"Quarrell","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Sheffield Children\u2019s Hospital, Western Bank, Sheffield S10 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Stals","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0713-4602","authenticated-orcid":false,"given":"Richard C","family":"Caswell","sequence":"additional","affiliation":[{"name":"University of Exeter School of Medicine, Barrack Road, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"De Franco","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Baple","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW, UK"},{"name":"University of Exeter School of Medicine, Barrack Road, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Burgess","sequence":"additional","affiliation":[{"name":"Department of Histology, Sheffield Children\u2019s Hospital NHS Foundation Trust, Western Bank, Sheffield UK. S10 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roobin","family":"Jokhi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Sheffield Teaching Hospitals, Jessop Wing Tree Root Walk, Sheffield S10 2SF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2080-3826","authenticated-orcid":false,"given":"Joshua L","family":"Heazlewood","sequence":"additional","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaka C","family":"Offiah","sequence":"additional","affiliation":[{"name":"University of Sheffield, Academic Unit of Child Health, Sheffield Children\u2019s Hospital NHS Foundation Trust, Western Bank, Sheffield S10 2TH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berit","family":"Ebert","sequence":"additional","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Ellard","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW, UK"},{"name":"University of Exeter School of Medicine, Barrack Road, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,19]]},"reference":[{"key":"2019122311002624200_ref1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/ajmg.1320250107","article-title":"A distinct lethal neonatal chondrodysplasia with snail-like pelvis: Schneckenbecken dysplasia","volume":"25","author":"Borochowitz","year":"1986","journal-title":"Am. J. Med. Genet."},{"key":"2019122311002624200_ref2","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1002\/ajmg.1320400429","article-title":"\u2018Snail-like pelvis\u2019 chondrodysplasia: a further case report","volume":"40","author":"Camera","year":"1991","journal-title":"Am. J. Med. Genet."},{"key":"2019122311002624200_ref3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s002470000357","article-title":"Schneckenbecken dysplasia, radiology, and histology","volume":"31","author":"Nikkels","year":"2001","journal-title":"Pediatr. Radiol."},{"key":"2019122311002624200_ref4","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/nm1655","article-title":"Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human","volume":"13","author":"Hiraoka","year":"2007","journal-title":"Nat. Med."},{"key":"2019122311002624200_ref5","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1002\/ajmg.a.37173","article-title":"A second locus for schneckenbecken dysplasia identified by a mutation in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1)","volume":"167","author":"Lee","year":"2015","journal-title":"Am. J. Med. Genet. A"},{"key":"2019122311002624200_ref6","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.mam.2012.12.004","article-title":"Roles of the nucleotide sugar transporters (SLC35 family) in health and disease","volume":"34","author":"Song","year":"2013","journal-title":"Mol. Aspects Med."},{"key":"2019122311002624200_ref7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0014-5793(01)02358-4","article-title":"Molecular characterization of human UDP-glucuronic acid\/UDP-N-acetylgalactosamine transporter, a novel nucleotide sugar transporter with dual substrate specificity","volume":"495","author":"Muraoka","year":"2001","journal-title":"FEBS Lett."},{"key":"2019122311002624200_ref8","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0959-440X(00)00125-1","article-title":"Recent advances in the study of the biosynthesis and functions of sulfated glycosaminoglycans","volume":"10","author":"Sugahara","year":"2000","journal-title":"Curr. Opin. Struct. 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