Amal Al Teneiji1, Theodora U J Bruun2, Sarah Sidky1, Dawn Cordeiro1, Ronald D Cohn3, Roberto Mendoza-Londono3, Mahendranath Moharir4, Julian Raiman5, Komudi Siriwardena6, Lianna Kyriakopoulou7, Saadet Mercimek-Mahmutoglu8. 1. Division of Clinical and Metabolic Genetics, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. 2. Division of Clinical and Metabolic Genetics, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada; Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Biochemistry, University of Oxford, Oxford, United Kingdom. 3. Division of Clinical and Metabolic Genetics, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada; Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada. 4. Division of Neurology, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. 5. Birmingham's Children Hospital, Birmingham, England. 6. Department of Medical Genetics, University of Alberta, Edmonton, Canada. 7. Division of Genome Diagnostics, Department of Paediatric Laboratory Medicine, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. 8. Division of Clinical and Metabolic Genetics, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada; Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada. Electronic address: saadet.mahmutoglu@sickkids.ca.
Abstract
BACKGROUND: Congenital disorders of glycosylation (CDG) are inborn defects of glycan metabolism. They are multisystem disorders. Analysis of transferrin isoforms is applied as a screening test for CDG type I (CDG-I) and type II (CDG-II). We performed a retrospective cohort study to determine spectrum of phenotype and genotype and prevalence of the different subtypes of CDG-I and CDG-II. MATERIAL AND METHODS: All patients with CDG-I and CDG-II evaluated in our institution's Metabolic Genetics Clinics were included. Electronic and paper patient charts were reviewed. We set-up a high performance liquid chromatography transferrin isoelectric focusing (TIEF) method to measure transferrin isoforms in our Institution. We reviewed the literature for the rare CDG-I and CDG-II subtypes seen in our Institution. RESULTS: Fifteen patients were included: 9 with PMM2-CDG and 6 with non-PMM2-CDG (one ALG3-CDG, one ALG9-CDG, two ALG11-CDG, one MPDU1-CDG and one ATP6V0A2-CDG). All patients with PMM2-CDG and 5 patients with non-PMM2-CDG showed abnormal TIEF suggestive of CDG-I or CDG-II pattern. In all patients, molecular diagnosis was confirmed either by single gene testing, targeted next generation sequencing for CDG genes, or by whole exome sequencing. CONCLUSION: We report 15 new patients with CDG-I and CDG-II. Whole exome sequencing will likely identify more patients with normal TIEF and expand the phenotypic spectrum of CDG-I and CDG-II. Crown
BACKGROUND:Congenital disorders of glycosylation (CDG) are inborn defects of glycan metabolism. They are multisystem disorders. Analysis of transferrin isoforms is applied as a screening test for CDG type I (CDG-I) and type II (CDG-II). We performed a retrospective cohort study to determine spectrum of phenotype and genotype and prevalence of the different subtypes of CDG-I and CDG-II. MATERIAL AND METHODS: All patients with CDG-I and CDG-II evaluated in our institution's Metabolic Genetics Clinics were included. Electronic and paper patient charts were reviewed. We set-up a high performance liquid chromatography transferrin isoelectric focusing (TIEF) method to measure transferrin isoforms in our Institution. We reviewed the literature for the rare CDG-I and CDG-II subtypes seen in our Institution. RESULTS: Fifteen patients were included: 9 with PMM2-CDG and 6 with non-PMM2-CDG (one ALG3-CDG, one ALG9-CDG, two ALG11-CDG, one MPDU1-CDG and one ATP6V0A2-CDG). All patients with PMM2-CDG and 5 patients with non-PMM2-CDG showed abnormal TIEF suggestive of CDG-I or CDG-II pattern. In all patients, molecular diagnosis was confirmed either by single gene testing, targeted next generation sequencing for CDG genes, or by whole exome sequencing. CONCLUSION: We report 15 new patients with CDG-I and CDG-II. Whole exome sequencing will likely identify more patients with normal TIEF and expand the phenotypic spectrum of CDG-I and CDG-II. Crown
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