{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T08:47:17Z","timestamp":1772095637713,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54NS115198"],"award-info":[{"award-number":["U54NS115198"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cosmc, encoded by the X\u2010linked\n                    <jats:italic>C1GALT1C1<\/jats:italic>\n                    , is a molecular chaperone in the endoplasmic reticulum and a master regulator of O\u2010glycosylation of mammalian glycoproteins. Recently, we described a germline mutation in\n                    <jats:italic>C1GALT1C1<\/jats:italic>\n                    in two male patients, giving rise to a congenital disorder of glycosylation\u2014\n                    <jats:italic>COSMC<\/jats:italic>\n                    \u2010CDG. Here, we have identified a female patient with a\n                    <jats:italic>de novo<\/jats:italic>\n                    mosaic variant in\n                    <jats:italic>C1GALT1C1<\/jats:italic>\n                    (c.202C&gt;T, p.Arg68*), which results in a truncated and nonfunctional form of Cosmc (Cosmc\u2010R68). The patient is mosaic, as ~27% of her buccal cells carry the mutation. The patient is now a 5\u2010year old who presented with nonimmune hydrops fetalis. As Cosmc is essential for the generation of normal O\u2010glycans through regulating T\u2010synthase activity, thereby enabling the formation of the universal Core 1 O\u2010glycan Gal\u03b21\u20103GalNAc\u03b11\u2010Ser\/Thr (T\u2010antigen), the loss of Cosmc leads to the expression of the unusual precursor O\u2010glycan termed Tn\u2010antigen (CD175) (GalNAc\u03b11\u2010Ser\/Thr). Owing to the mutational mosaicism, only a significant minority of cells would exhibit abnormal O\u2010glycosylation. Analysis of red blood cells (RBCs), leukocytes, and serum from this patient indicated reduced expression of Cosmc and T\u2010synthase proteins and lower T\u2010synthase activity. Consistent with these findings, we observed reduced normal O\u2010glycans in serum glycoproteins and RBCs from the patient, along with elevated expression of the Tn\u2010antigen in serum glycoproteins compared to controls. This case represents the first description of a true mosaic loss\u2010of\u2010function variant in\n                    <jats:italic>C1GALT1C1<\/jats:italic>\n                    , that is, one that occurred postzygotically during embryogenesis, and raises interesting questions about the role of O\u2010glycosylation during fetal development and its consequences on the clinical presentation.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70006","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T01:39:56Z","timestamp":1739497196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>\n                      <i>C1GALT1C1<\/i>\n                    <\/scp>\n                    \u2010Associated Mosaic Disorder of Glycosylation in a Female"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8718-636X","authenticated-orcid":false,"given":"Rajindra P.","family":"Aryal","sequence":"first","affiliation":[{"name":"Department of Surgery Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditya","family":"Ramanujan","sequence":"additional","affiliation":[{"name":"Department of Surgery Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Bucci","sequence":"additional","affiliation":[{"name":"Department of Surgery Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Neckelmann","sequence":"additional","affiliation":[{"name":"Helen DeVos Children's Hospital Medical Genetics  Grand Rapids Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4987-3016","authenticated-orcid":false,"given":"Jamie","family":"Heimburg\u2010Molinaro","sequence":"additional","affiliation":[{"name":"Department of Surgery Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra F.","family":"Cummings","sequence":"additional","affiliation":[{"name":"Department of Surgery Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Erger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics and Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bodo B.","family":"Beck","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics and Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie H.","family":"Seaver","sequence":"additional","affiliation":[{"name":"Helen DeVos Children's Hospital Medical Genetics  Grand Rapids Michigan USA"},{"name":"Department of Pediatrics and Human Development Michigan State University College of Human Medicine  Grand Rapids Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8918-5034","authenticated-orcid":false,"given":"Richard D.","family":"Cummings","sequence":"additional","affiliation":[{"name":"Department of Surgery Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"715","article-title":"Genetics of Glycosylation in Mammalian Development and Disease","volume":"25","author":"Stanley P.","year":"2024","journal-title":"Nature Reviews. 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