- Title
- ALG1-CDG: clinical and molecular characterization of 39 unreported patients
- Creator
- Ng, Bobby G.; Shiryaev, Sergey A.; Barone, Rita; Berry, Gerard T.; Brumbaugh, Jane E.; Buckingham, Kati J.; Clarkson, Katie; Cole, F. Sessions; O'Connor, Shawn; Cooper, Gregory M.; Van Coster, Rudy; Demmer, Laurie A.; Rymen, Daisy; Diogo, Luisa; Fay, Alexander J.; Ficicioglu, Can; Fiumara, Agata; Gahl, William A.; Ganetzky, Rebecca; Goel, Himanshu; Harshman, Lyndsay A.; He, Miao; Jaeken, Jaak; Eklund, Erik A.; James, Philip M.; Katz, Daniel; Keldermans, Liesbeth; Kibaek, Maria; Kornberg, Andrew J.; Lachlan, Katherine; Lam, Christina; Yaplito-Lee, Joy; Nickerson, Deborah A.; Peters, Heidi L.; Raymond, Kimiyo; Race, Valerie; Régal, Luc; Rush, Jeffrey S.; Rutledge, S. Lane; Shendure, Jay; Souche, Erika; Sparks, Susan E.; Trapane, Pamela; Sanchez-Valle, Amarillis; Vilain, Eric; Kircher, Martin; Vøllo, Arve; Waechter, Charles J.; Wang, Raymond Y.; Wolfe, Lynne A.; Wong, Derek A.; Wood, Tim; Yang, Amy C.; Matthijs, Gert; Freeze, Hudson H.; University of Washington Center for Mendelian Genomics; Abdenur, Jose E.; Alehan, Fusun; Midro, Alina T.; Bamshad, Michael J.
- Relation
- Human Mutation Vol. 37, Issue 7, p. 653-660
- Publisher Link
- http://dx.doi.org/10.1002/humu.22983
- Publisher
- Wiley-Blackwell Publishing
- Resource Type
- journal article
- Date
- 2016
- Description
- Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over 100 genes leading to impaired protein or lipid glycosylation. ALG1 encodes a ß1,4 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.
- Subject
- CDG; asparagine-linked glycosylation protein 1; carbohydrate-deficient transferrin; xeno-tetrasaccharide
- Identifier
- http://hdl.handle.net/1959.13/1341483
- Identifier
- uon:28748
- Identifier
- ISSN:1059-7794
- Language
- eng
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