{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:01:33Z","timestamp":1791576093364,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The congenital disorder of glycosylation associated with <jats:italic>ALG1<\/jats:italic> (ALG1\u2010CDG) is a rare autosomal recessive disease. Due to the deficiency of \u03b21,4 mannosyltransferase caused by pathogenic variants in <jats:italic>ALG1<\/jats:italic> gene, the assembly and processing of glycans in the protein glycosylation pathway are impaired, resulting in a broad clinical spectrum with multi\u2010organ involvement. To raise awareness of clinicians for its manifestations and genotype, we here reported a new patient with a novel variant in <jats:italic>ALG1<\/jats:italic> gene and reviewed the literature to study the genotype\u2013phenotype correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Clinical characteristics were collected, and clinical exome sequencing was used to identify the causative variants. MutationTaster, PyMol, and FoldX were used to predict the pathogenicity, changes in 3D model molecular structure of protein, and changes of free energy caused by novel variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The proband was a 13\u2010month\u2010old Chinese Han male characterized by epileptic seizures, psychomotor development delay, muscular hypotonia, liver and cardiac involvement. Clinical exome sequencing revealed the biallelic compound heterozygosity variants, a previously reported variant c.434G&gt;A (p.G145N, paternal) and a novel variant c.314T&gt;A (p.V105N, maternal). The literature review found that in severe phenotypes, the incidences of clinical manifestations were significantly higher than that in mild phenotypes, including congenital nephrotic syndrome, agammaglobulinemia, and severe hydrops. Homozygous c.773C&gt;T was a strongly pathogenic variant associated with a severe phenotype. When heterozygous for c.773C&gt;T, patients with another variant leading to substitution in amino acids within the strongly conserved regions (c.866A&gt;T, c.1025A&gt;C, c.1182C&gt;G) may cause a more severe phenotype than those within less\u2010conserved regions (c.434G&gt;A, c.450C&gt;G, c.765G&gt;A, c.1287T&gt;A). c.1129A&gt;G, c.1076C&gt;T, and c.1287T&gt;A were more likely to be associated with a mild phenotype. The assessment of disease phenotypes requires a combination of genotype and clinical manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The case reported herein adds to the mutations identified in ALG1\u2010CDG and a review of this literature expands the study of the phenotypic and genotypic spectrum of this disorder.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2197","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T10:55:41Z","timestamp":1684493741000},"source":"Crossref","is-referenced-by-count":8,"title":["A novel variant in <i>ALG1<\/i> gene associated with congenital disorder of glycosylation: A case report and short literature review"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7893-4124","authenticated-orcid":false,"given":"Yan","family":"Xue","sequence":"first","affiliation":[{"name":"Tianjin Pediatric Research Institute Tianjin Children's Hospital (Tianjin University Children's Hospital)  Tianjin China"},{"name":"Tianjin Key Laboratory of Birth Defects for Prevention and Treatment  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tianjin Medical University  Tianjin China"},{"name":"Department of Pediatrics Maternal and Child Health Hospital of Tangshan  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Children's Hospital (Tianjin University Children's Hospital)  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-4537","authenticated-orcid":false,"given":"Jianbo","family":"Shu","sequence":"additional","affiliation":[{"name":"Tianjin Pediatric Research Institute Tianjin Children's Hospital (Tianjin University Children's Hospital)  Tianjin China"},{"name":"Tianjin Key Laboratory of Birth Defects for Prevention and Treatment  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Yan","sequence":"additional","affiliation":[{"name":"Tianjin Pediatric Research Institute Tianjin Children's Hospital (Tianjin University Children's Hospital)  Tianjin China"},{"name":"Tianjin Key Laboratory of Birth Defects for Prevention and Treatment  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Children's Hospital (Tianjin University Children's Hospital)  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Children's Hospital (Tianjin University Children's Hospital)  Tianjin 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