dc.contributor.author | Alehan, Fusun | |
dc.date.accessioned | 2019-08-08T07:36:16Z | |
dc.date.available | 2019-08-08T07:36:16Z | |
dc.date.issued | 2016 | |
dc.identifier.issn | 1059-7794 | |
dc.identifier.uri | http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC4907823&blobtype=pdf | |
dc.identifier.uri | http://hdl.handle.net/11727/3833 | |
dc.description.abstract | Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over 100 genes leading to impaired protein or lipid glycosylation. ALG1 encodes a beta 1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date 13 mutations in 18 patients from 14 families have been described with varying degrees of clinical severity. We identified and characterized 39 previously unreported cases of ALG1-CDG from 32 families and add 26 new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2, was seen in all 27 patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder. (C) 2016 Wiley Periodicals, Inc. | en_US |
dc.language.iso | eng | en_US |
dc.relation.isversionof | 10.1002/humu.22983 | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | CDG | en_US |
dc.subject | asparagine-linked glycosylation protein 1 | en_US |
dc.subject | carbohydrate-deficient transferrin | en_US |
dc.subject | xeno-tetrasaccharide | en_US |
dc.title | ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients | en_US |
dc.type | article | en_US |
dc.relation.journal | HUMAN MUTATION | en_US |
dc.identifier.volume | 37 | en_US |
dc.identifier.issue | 7 | en_US |
dc.identifier.startpage | 653 | en_US |
dc.identifier.endpage | 660 | en_US |
dc.identifier.wos | 000379934200004 | en_US |
dc.identifier.scopus | 2-s2.0-84974730910 | en_US |
dc.contributor.pubmedID | 26931382 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi | en_US |