講演情報
[O30-2]MOGS-CDGの臨床的、生化学的および遺伝学的特徴：まれな先天性糖鎖合成異常症
○島田 姿野1,2, Bobby Ng3, Amy White4, Kim Nickander4, Christina Lam5, Esperanza Font-Montgomery6, Charles Lourenco7, Miao He8, Luis Umana9, Devon Haynes10, Heather Byers11, Rani Sachdev12, Stephen Malone13, Ingrid Scheffer14, David Adams2, William Gahl2, May Malicdan2, Kimiyo Raymond4, Hudson Freeze3, Lynne Wolfe2 (1.順天堂大学医学部付属静岡病院, 2.Medical Genetic Branch, National Human Genome Research Institute, Bethesda, USA, 3.Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA, 4.Biochemical Genetics Laboratory, Mayo Clinic Department of Laboratory Medicine and Pathology, Rochester, Minnesota, USA, 5.Division of Genetic Medicine, Department of Pediatrics, Seattle Childrens Hospital, Seattle, Washington, USA, 6.University Hospital Medical Genetics Clinic, University of Missouri, Columbia, Missouri, USA, 7.Department of Medical Genetics, School of Medicine, Neurogenetics Unit, University of Sao Paulo, Sao Paulo, Brazil, 8.Department of Pathology and Laboratory Medicine, The Childrens Hospital of Philadelphia, Philadelphia, Pennsylvania, USA, 9.Division of Genetics and Metabolism, Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, Texas, USA, 10.Division of Genetics, Arnold Palmer Hospital for Children, Orland, Florida, USA, 11.Division of Medical Genetics, Stanford University, Stanford, California, USA, 12.Center for Clinical Genetics, Sydney Childrens Hospital Randwick, Randwick, New South Wales, Australia, 13.Department of Neurosciences, Queensland Childrens Hospital, South Brisbane, Queensland, Australia, 14.Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia)
【Purpose】 To summarise the clinical, molecular and biochemical phenotype of mannosyl-oligosaccharide glucosidase-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 characterization 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 variableseverity. 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 screeningand confirmation of disease.