TY - JOUR
T1 - Clinical, biochemical and genetic characteristics of MOGS-CDG
T2 - a rare congenital disorder of glycosylation
AU - Shimada, Shino
AU - Ng, Bobby G.
AU - White, Amy L.
AU - Nickander, Kim K.
AU - Turgeon, Coleman
AU - Liedtke, Kristen L.
AU - Lam, Christina T.
AU - Font-Montgomery, Esperanza
AU - Lourenco, Charles M.
AU - He, Miao
AU - Peck, Dawn S.
AU - Umana, Luis A.
AU - Uhles, Crescenda L.
AU - Haynes, Devon
AU - Wheeler, Patricia G.
AU - Bamshad, Michael J.
AU - Nickerson, Deborah A.
AU - Cushing, Tom
AU - Gates, Ryan
AU - Gomez-Ospina, Natalia
AU - Byers, Heather M.
AU - Scalco, Fernanda B.
AU - Martinez, Noelia N.
AU - Sachdev, Rani
AU - Smith, Lacey
AU - Poduri, Annapurna
AU - Malone, Stephen
AU - Harris, Rebekah V.
AU - Scheffer, Ingrid E.
AU - Rosenzweig, Sergio D.
AU - Adams, David R.
AU - Gahl, William A.
AU - Malicdan, May Christine V.
AU - Raymond, Kimiyo M.
AU - Freeze, Hudson H.
AU - Wolfe, Lynne A.
N1 - Funding Information:
This research was supported by the Intramural Research Programme of the National Human Genome Research Institute and the Common Fund of the NIH Office of the Director. The Freeze Lab was supported by The Rocket Fund, and NIH R01DK99551. SS was partly supported by the JSPS Research fellowship for Japanese Biomedical and Behaviour Research. RK, MH and HHF are partially supported by the NINDS/NCATS Frontiers in Congenital Disorders of Glycosylation Grant (1U54NS115198-01). IS is supported by the National Health and Medical Research Council of Australia. University of Washington Centre for Mendelian Genomics (UW-CMG) was funded by NHGRI and NHLBI grants UM1 HG006493 and U24 HG008956.
Publisher Copyright:
© 2022 BMJ Publishing Group. All rights reserved.
PY - 2022/7/5
Y1 - 2022/7/5
N2 - 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.
AB - 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.
KW - central nervous system diseases
KW - diagnosis
KW - glycomics
KW - human genetics
KW - sequence analysis, DNA
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U2 - 10.1136/jmedgenet-2021-108177
DO - 10.1136/jmedgenet-2021-108177
M3 - Article
C2 - 35790351
AN - SCOPUS:85134651721
SN - 0022-2593
VL - 59
SP - 1104
EP - 1115
JO - Journal of medical genetics
JF - Journal of medical genetics
IS - 11
ER -