title: Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Amal
authors.initials: A
authors.lastname: Al Teneiji
authors.affiliation: 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.
authors.forename: Theodora U J
authors.initials: TU
authors.lastname: Bruun
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sidky
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Dawn
authors.initials: D
authors.lastname: Cordeiro
authors.affiliation: 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.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Cohn
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mendoza-Londono
authors.affiliation: Division of Neurology, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Mahendranath
authors.initials: M
authors.lastname: Moharir
authors.affiliation: Birmingham's Children Hospital, Birmingham, England.
authors.forename: Julian
authors.initials: J
authors.lastname: Raiman
authors.affiliation: Department of Medical Genetics, University of Alberta, Edmonton, Canada.
authors.forename: Komudi
authors.initials: K
authors.lastname: Siriwardena
authors.affiliation: Division of Genome Diagnostics, Department of Paediatric Laboratory Medicine, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lianna
authors.initials: L
authors.lastname: Kyriakopoulou
authors.affiliation: 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.
authors.forename: Saadet
authors.initials: S
authors.lastname: Mercimek-Mahmutoglu
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D018981:Congenital Disorders of Glycosylation / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D059472:Exome; D005260:Female; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D020033:Protein Isoforms / Q000378:metabolism; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA / Q000379:methods*; D014168:Transferrin / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D014168:Transferrin
keywords: Combined N- and O-glycosylation; Congenital disorders of glycosylation; N-glycosylation; Transferrin isoelectric focusing