{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:03:12Z","timestamp":1790798592366,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Congenital disorders of glycosylation (CDG) are a heterogeneous group of metabolic diseases caused by defects in glycan biosynthesis, predominantly affecting the N\u2010glycosylation pathway. Pathogenic variants in the DDOST gene, encoding a non\u2010catalytic subunit of the oligosaccharyltransferase (OST) complex, underlie an ultra\u2010rare CDG subtype with only three patients reported to date, complicating diagnosis and genotype\u2013phenotype correlations. We describe a female patient with developmental delay, hypotonia, and dysmorphic features. Genetic analyses included chromosomal microarray, FMR1 testing, and trio\u2010based next\u2010generation sequencing with a neurodevelopmental disorder panel. Variants were assessed using ACMG criteria, population databases, segregation, and in silico analysis. We also reviewed published\n                    <jats:italic>DDOST<\/jats:italic>\n                    \u2010CDG cases to compare clinical and molecular findings. Compound heterozygous\n                    <jats:italic>DDOST<\/jats:italic>\n                    variants were identified: (i) a maternally inherited 413\u2010kb deletion encompassing exons 3\u201311, predicted to abolish gene function, and (ii) a paternally inherited in\u2010frame deletion (p.Lys435del), removing a highly conserved residue in the luminal C\u2010terminal domain. Both were absent from population databases and classified as pathogenic or likely pathogenic, consistent with autosomal recessive inheritance. Metabolic testing confirmed a type I transferrin isoform pattern, supporting a congenital disorder of glycosylation. This report expands the genetic and phenotypic spectrum of\n                    <jats:italic>DDOST<\/jats:italic>\n                    \u2010CDG by describing the first structural variant. Review of published cases highlights hypotonia and motor delay as consistent features, while other traits such as strabismus, feeding difficulties, or hepatic dysfunction appear variable. Our findings underscore the clinical heterogeneity of\n                    <jats:italic>DDOST<\/jats:italic>\n                    \u2010CDG and the complementary role of metabolic and genomic testing.\n                  <\/jats:p>","DOI":"10.1002\/ajmga.70026","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T08:30:47Z","timestamp":1765787447000},"page":"1069-1076","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>DDOST<\/scp>\n                    \u2010Congenital Disorder of Glycosylation: Defining the Clinical Spectrum and First Report of a Structural Variant"],"prefix":"10.1002","volume":"200","author":[{"given":"Giuseppe","family":"Reynolds","sequence":"first","affiliation":[{"name":"Postgraduate School of Pediatrics, Department of Public Health and Pediatrics University of Turin  Turin Italy"},{"name":"Department of Public Health and Pediatrics University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Carelli","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Rondot","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Massuras","sequence":"additional","affiliation":[{"name":"Pediatric Clinical Genetics Regina Margherita Children's Hospital  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Pagliardini","sequence":"additional","affiliation":[{"name":"Pediatric Inborn Errors of Metabolism, Department of Pediatrics Regina Margherita Children's Hospital  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-652X","authenticated-orcid":false,"given":"Vincenza","family":"Gragnaniello","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Department of Women's and Children's Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-137X","authenticated-orcid":false,"given":"Alberto B.","family":"Burlina","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Department of Women's and Children's Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Resciniti","sequence":"additional","affiliation":[{"name":"Research &amp; Innovation (R&amp;I Genetics) Srl  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Agata","sequence":"additional","affiliation":[{"name":"Research &amp; Innovation (R&amp;I Genetics) Srl  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Colavito","sequence":"additional","affiliation":[{"name":"Research &amp; Innovation (R&amp;I Genetics) Srl  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-6013","authenticated-orcid":false,"given":"Alessandro","family":"Mussa","sequence":"additional","affiliation":[{"name":"Department of Public Health and Pediatrics University of Turin  Turin Italy"},{"name":"Pediatric Clinical Genetics Regina Margherita Children's Hospital  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100034\u20101387197"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.108253"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12565"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010023\u201002879\u2010z"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23829"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000031921.02259.35"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24309"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.6.833"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000323812.40708.1f"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.12.024"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010011\u20109337\u20101"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010016\u20109945\u2010x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2018.03.002"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010021\u201000974\u20102"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12111658"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10113022"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23798"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2021.129976"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac373"},{"key":"e_1_2_12_22_1","doi-asserted-by":"crossref","unstructured":"Yamagata T. T.Tsuru M. Y.Momoi et\u00a0al.1997.Genome Organization of Human 48\u2010KDa Oligosaccharyltransferase (DDOST) 45.","DOI":"10.1006\/geno.1997.4966"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmga.70026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmga.70026","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmga.70026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:44:59Z","timestamp":1787892299000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmga.70026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,15]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/ajmga.70026"],"URL":"https:\/\/doi.org\/10.1002\/ajmga.70026","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,15]]},"assertion":[{"value":"2025-10-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}