Clinical, biochemical and genetic characteristics of MOGS-CDG: a rare congenital disorder of glycosylation. Issue 11 (5th July 2022)

• Record Type: Journal Article
• Authors: Shimada, Shino; Ng, Bobby G; White, Amy L; Nickander, Kim K; Turgeon, Coleman; Liedtke, Kristen L; Lam, Christina T; Font-Montgomery, Esperanza; Lourenco, Charles M; He, Miao; Peck, Dawn S; Umana, Luis A; Uhles, Crescenda L; Haynes, Devon; Wheeler, Patricia G; Bamshad, Michael J; Nickerson, Deborah A; Cushing, Tom; Gates, Ryan; Gomez-Ospina, Natalia; Byers, Heather M; Scalco, Fernanda B; Martinez, Noelia N; Sachdev, Rani; Smith, Lacey; Poduri, Annapurna; Malone, Stephen; Harris, Rebekah V; Scheffer, Ingrid E; Rosenzweig, Sergio D; Adams, David R; Gahl, William A; Malicdan, May Christine V; Raymond, Kimiyo M; Freeze, Hudson H; Wolfe, Lynne A;
• Other Names: author non-byline.; Bamshad Michael J author non-byline.; Nickerson Deborah A author non-byline.; Anderson Peter author non-byline.; Bacus Tamara J author non-byline.; Blue Elizabeth E author non-byline.; Brower Katherine author non-byline.; Buckingham Kati J author non-byline.; Chong Jessica X author non-byline.; Davis Colleen P author non-byline.; Davis Chayna J author non-byline.; Frazar Christian D author non-byline.; Gomeztagle-Burgess Katherine author non-byline.; Gordon William W author non-byline.; Horike-Pyne Martha author non-byline.; Hurless Jameson R author non-byline.; Jarvik Gail P author non-byline.; Johanson Eric author non-byline.; Thomas Kolar J author non-byline.; Marvin Colby T author non-byline.; McGee Sean author non-byline.; McGoldrick Daniel J author non-byline.; Mekonnen Betselote author non-byline.; Nielsen Patrick M author non-byline.; Patterson Karynne author non-byline.; Radhakrishnan Aparna author non-byline.; Richardson Matthew A author non-byline.; Roote Gwendolin T author non-byline.; Ryke Erica L author non-byline.; Shively Kathryn M author non-byline.; Smith Joshua D author non-byline.; Tackett Monica author non-byline.; Weiss Jeffrey M author non-byline.; Wheeler Marsha M author non-byline.; Yi Qian author non-byline.; Zhang Xiaohong author non-byline.;
• Is Part Of: Journal of medical genetics. Volume 59:Issue 11(2022)
• Page Start: 1104
• Page End: 1115
• Publication Date: 2022-07-05
• Subjects: human genetics -- sequence analysis, DNA -- central nervous system diseases -- diagnosis -- glycomics; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2021-108177
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Purpose: To summarise the clinical, molecular and biochemical phenotype of mannosyl-oligosaccharide glucosidase-related congenital disorders of glycosylation (MOGS-CDG), which presents with variable clinical manifestations, and to analyse which clinical biochemical assay consistently supports diagnosis in individuals with bi-allelic variants in MOGS . Methods: Phenotypic characterisation was performed through an international and multicentre collaboration. Genetic testing was done by exome sequencing and targeted arrays. Biochemical assays on serum and urine were performed to delineate the biochemical signature of MOGS-CDG. Results: Clinical phenotyping revealed heterogeneity in MOGS-CDG, including neurological, immunological and skeletal phenotypes. Bi-allelic variants in MOGS were identified in 12 individuals from 11 families. The severity in each organ system was variable, without definite genotype correlation. Urine oligosaccharide analysis was consistently abnormal for all affected probands, whereas other biochemical analyses such as serum transferrin analysis was not consistently abnormal. Conclusion: The clinical phenotype of MOGS-CDG includes multisystemic involvement with variable severity. Molecular analysis, combined with biochemical testing, is important for diagnosis. In MOGS-CDG, urine oligosaccharide analysis via matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry can be used as a reliable biochemical test for screening and confirmation of disease.