{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T08:03:27Z","timestamp":1783238607699,"version":"3.54.6"},"reference-count":32,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1U54NS115198"],"award-info":[{"award-number":["1U54NS115198"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009053","name":"Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","award":["IA\/CRC\/20\/1\/600002"],"award-info":[{"award-number":["IA\/CRC\/20\/1\/600002"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Asparagine\u2010linked glycosylation 1 protein is a \u03b2\u20101,4\u2010mannosyltransferase, is encoded by the <jats:italic>ALG1<\/jats:italic> gene, which catalyzes the first step of mannosylation in N\u2010glycosylation. Pathogenic variants in <jats:italic>ALG1<\/jats:italic> cause a rare autosomal recessive disorder termed as ALG1\u2010CDG. We performed a quantitative proteomics and N\u2010glycoproteomics study in fibroblasts derived from patients with one homozygous and two compound heterozygous pathogenic variants in <jats:italic>ALG1<\/jats:italic>. Several proteins that exhibited significant upregulation included insulin\u2010like growth factor II and pleckstrin, whereas hyaluronan and proteoglycan link protein 1 was downregulated. These proteins are crucial for cell growth, survival and differentiation. Additionally, we observed a decrease in the expression of mitochondrial proteins and an increase in autophagy\u2010related proteins, suggesting mitochondrial and cellular stress. N\u2010glycoproteomics revealed the reduction in high\u2010mannose and complex\/hybrid glycopeptides derived from numerous proteins in patients explaining that defect in <jats:italic>ALG1<\/jats:italic> has broad effects on glycosylation. Further, we detected an increase in several short oligosaccharides, including chitobiose (HexNAc<jats:sub>2<\/jats:sub>) trisaccharides (Hex\u2010HexNAc<jats:sub>2<\/jats:sub>) and novel tetrasaccharides (NeuAc\u2010Hex\u2010HexNAc<jats:sub>2<\/jats:sub>) derived from essential proteins including LAMP1, CD44 and integrin. These changes in glycosylation were observed in all patients irrespective of their gene variants. Overall, our findings not only provide novel molecular insights into understanding ALG1\u2010CDG but also offer short oligosaccharide\u2010bearing peptides as potential biomarkers.<\/jats:p>","DOI":"10.1002\/pmic.202400012","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T09:23:56Z","timestamp":1710235436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dysregulated proteome and N\u2010glycoproteome in ALG1\u2010deficient fibroblasts"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4209-2180","authenticated-orcid":false,"given":"Rohit","family":"Budhraja","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"},{"name":"Manipal Academy of Higher Education  Manipal Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Radenkovic","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamas","family":"Kozicz","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Morava","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9943-6127","authenticated-orcid":false,"given":"Akhilesh","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"},{"name":"Manipal Academy of Higher Education  Manipal Karnataka India"},{"name":"Center for Individualized Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22983"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)81096-7"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/382493"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh050"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/382492"},{"key":"e_1_2_11_7_1","first-page":"103","volume-title":"Essentials of glycobiology","author":"Stanley P.","year":"2022"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.10.013"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-2711"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01657-5"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2015.243279"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9884-y"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1MO00132A"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12557"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26245"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01306-0"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1011"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3901"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00710-w"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu393"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c02513"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.1c00391"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14081585"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2023.01.004"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24031937"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.9"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12446"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20580"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(75)90167-8"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwy112"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.03.003"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000387"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2023.107610"}],"container-title":["PROTEOMICS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pmic.202400012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T09:54:53Z","timestamp":1761040493000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/pmic.202400012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,12]]},"references-count":32,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/pmic.202400012"],"URL":"https:\/\/doi.org\/10.1002\/pmic.202400012","archive":["Portico"],"relation":{},"ISSN":["1615-9853","1615-9861"],"issn-type":[{"value":"1615-9853","type":"print"},{"value":"1615-9861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,12]]},"assertion":[{"value":"2024-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2400012"}}