{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:03:13Z","timestamp":1790798593411,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["2T32GM082773-16"],"award-info":[{"award-number":["2T32GM082773-16"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1U54NS115198-05"],"award-info":[{"award-number":["1U54NS115198-05"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>STT3A encodes the catalytic subunit of the oligosaccharyltransferase A (OST-A) complex and is classically linked to severe autosomal-recessive congenital disorder of glycosylation (CDG). To define the distinct autosomal-dominant disorder, we reviewed all published cases and integrated three previously unpublished individuals from the CDG natural history study. Across 21 individuals, abnormal transferrin glycosylation was present in nearly all individuals (20\/21), and subtle facial dysmorphism was common (18\/21). Neurodevelopmental involvement was frequent, including motor delay (13\/21), learning difficulties (13\/21), speech delay (12\/21), and intellectual disability (10\/21). Musculoskeletal manifestations were also common, including skeletal abnormalities (12\/21), short stature (11\/21), muscle cramps (8\/21), and early-onset osteoarthritis in adults (6\/21). Less frequent features included congenital heart defects (5\/21) and coagulation factor deficiency (5\/21). Importantly, the newly reported individuals expand dominant STT3A-CDG with previously unreported features, including anorectal malformation, morbid obesity, and clinically significant bleeding diathesis with von Willebrand factor and factor VIII deficiency. Biochemical signatures ranged from classic type I transferrin patterns to subtle or atypical abnormalities, emphasizing that near-normal transferrin testing does not exclude the diagnosis. Variants clustered in conserved catalytic regions, with recurrent p.Arg405 across de novo, inherited, and mosaic cases supporting a mutational hotspot and likely dominant-negative mechanism.<\/jats:p>","DOI":"10.3390\/biom16030418","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:12:24Z","timestamp":1773321144000},"page":"418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Expanded Clinical Spectrum of Autosomal-Dominant STT3A-CDG"],"prefix":"10.3390","volume":"16","author":[{"given":"Hamdan","family":"Al-Shahrani","sequence":"first","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5832-8832","authenticated-orcid":false,"given":"Evelin","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, University of P\u00e9cs Medical School, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Staccone","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2114-0494","authenticated-orcid":false,"given":"Georgia","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7278-8242","authenticated-orcid":false,"given":"Yutaka","family":"Furuta","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Schecter","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Edmondson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"McRae","sequence":"additional","affiliation":[{"name":"Division of Genetics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3178-2848","authenticated-orcid":false,"given":"Josh","family":"Baker","sequence":"additional","affiliation":[{"name":"Division of Genetics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7441-700X","authenticated-orcid":false,"given":"Eva","family":"Morava","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Biophysics, University of P\u00e9cs Medical School, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7093-8844","authenticated-orcid":false,"given":"Rory J.","family":"Tinker","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1186\/s13023-023-02879-z","article-title":"Congenital disorders of glycosylation (CDG): State of the art in 2022","volume":"18","author":"Francisco","year":"2023","journal-title":"Orphanet J. 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