{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:02:29Z","timestamp":1791576149630,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2703900"],"award-info":[{"award-number":["2022YFC2703900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital disorders of glycosylation (CDG) are a type of inborn error of metabolism (IEM) resulting from defects in glycan synthesis or failed attachment of glycans to proteins or lipids. One rare type of CDG is caused by homozygous or compound heterozygous loss\u2010of\u2010function variants in mannosidase alpha class 2B member 2 (<jats:italic>MAN2B2<\/jats:italic>). To date, only two cases of <jats:italic>MAN2B2<\/jats:italic>\u2010CDG have been reported worldwide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Trio whole\u2010exome sequencing (Trio\u2010WES) was conducted to screen for candidate variants. N\u2010glycan profiles were measured by liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS). <jats:italic>MAN2B2<\/jats:italic> expression was evaluated by western blotting. MX dynamin like GTPase 1 (<jats:italic>MX1<\/jats:italic>) function was estimated via Thogoto virus (THOV) minireplicon assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Trio\u2010WES identified compound heterozygous <jats:italic>MAN2B2<\/jats:italic> (hg19, NM_015274.1) variants (c.384G&gt;T; c.926T&gt;A) in a CDG patient. This patient exhibited metabolic abnormalities, symptoms of digestive tract dysfunction, infection, dehydration, and seizures. Novel immune dysregulation characterized by abnormal lymphocytes and immunoglobulin was observed. The MAN2B2 protein level was not affected, while LC\u2013MS\/MS showed obvious disruption of N\u2010glycans and N\u2010linked glycoproteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We described a CDG patient with novel phenotypes and disruptive N\u2010glycan profiling caused by compound heterozygous <jats:italic>MAN2B2<\/jats:italic> variants (c.384G&gt;T; c.926T&gt;A). Our findings broadened both the genetic and clinical spectra of CDG.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2422","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T05:10:16Z","timestamp":1713244216000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Congenital disorders of glycosylation with multiorgan disruption and immune dysregulation caused by compound heterozygous variants in <scp><i>MAN2B2<\/i><\/scp>"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-0451","authenticated-orcid":false,"given":"Shiqi","family":"Fan","sequence":"first","affiliation":[{"name":"McKusick\u2010Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology The Affiliated Hospital of Capital Institute of Pediatrics  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Wang","sequence":"additional","affiliation":[{"name":"McKusick\u2010Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9566-9003","authenticated-orcid":false,"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology The Affiliated Hospital of Capital Institute of Pediatrics  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[{"name":"McKusick\u2010Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwx036"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010022\u201001352\u2010z"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12250\u2010010\u20103147\u20108"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2023.107582"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.211326"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072092"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.12.003"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010022\u201002422\u20106"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7768"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.05.012"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.04.007"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010018\u20100063\u20106"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20103\u201021"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.09.005"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2020.129751"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M508930200"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.1.129"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2868"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010022\u201001125\u20107"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11605\u2010021\u201005087\u2010x"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.11.016"}],"container-title":["Molecular Genetics &amp; 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