title: A Population-Based Study on Congenital Disorders of Protein N- and Combined with O-Glycosylation Experience in Clinical and Genetic Diagnosis.
abstract: To describe the clinical, biochemical, and genetic features of patients with congenital disorders of glycosylation (CDG) identified in Spain during the last 20 years.
  
  
  
  Patients were selected among those presenting with multisystem disease of unknown etiology. The isoforms of transferrin and of ApoC3 and dolichols were analyzed in serum; phosphomannomutase and mannosephosphate isomerase activities were measured in fibroblasts. Conventional or massive parallel sequencing (customized panel or Illumina Clinical-Exome Sequencing TruSight One Gene Panel) was used to identify genes and mutations.
  
  
  
  Ninety-seven patients were diagnosed with 18 different CDG. Eighty-nine patients had a type 1 transferrin profile; 8 patients had a type 2 transferrin profile, with 6 of them showing an alteration in the ApoC3 isoform profile. A total of 75% of the patients had PMM2-CDG presenting with a heterogeneous mutational spectrum. The remaining patients showed mutations in any of the following genes: MPI, PGM1, GFPT1, SRD5A3, DOLK, DPGAT1, ALG1, ALG6, RFT1, SSR4, B4GALT1, DPM1, COG6, COG7, COG8, ATP6V0A2, and CCDC115.
  
  
  
  Based on literature and on this population-based study of CDG, a comprehensive scheme including reported clinical signs of CDG is offered, which will hopefully reduce the timeframe from clinical suspicion to genetic confirmation. The different defects of CDG identified in Spain have contributed to expand the knowledge of CDG worldwide. A predominance of PMM2 deficiency was detected, with 5 novel PMM2 mutations being described.
authors.affiliation: Center of Molecular Biology-Severo Ochoa, University Autonomous of Madrid-Spanish National Research Council, La Paz Institute for Health Research, Center for Biomedical Research on Rare Diseases, Madrid, Spain. Electronic address: Celia.perez@uam.es.
authors.forename: Celia
authors.initials: C
authors.lastname: Pérez-Cerdá
authors.affiliation: Inborn Errors of Metabolism, Biochemical and Molecular Genetics Serv., Biomedical Diagnostic Center, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, Center for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors.forename: Ma Luisa
authors.initials: ML
authors.lastname: Girós
authors.affiliation: Department of Pediatric Neurology, Institute of Pediatric Research-Hospital Sant Joan de Déu, Center for Biomedical Research on Rare Diseases, Barcelona, Spain; Department of Clinical Biochemistry, Institute of Pediatric Research-Hospital Sant Joan de Déu, Centre for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Serrano
authors.affiliation: Center of Molecular Biology-Severo Ochoa, University Autonomous of Madrid-Spanish National Research Council, La Paz Institute for Health Research, Center for Biomedical Research on Rare Diseases, Madrid, Spain.
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Ecay
authors.affiliation: Inborn Errors of Metabolism, Biochemical and Molecular Genetics Serv., Biomedical Diagnostic Center, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, Center for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Gort
authors.affiliation: Department of Pediatric Neurology, Institute of Pediatric Research-Hospital Sant Joan de Déu, Center for Biomedical Research on Rare Diseases, Barcelona, Spain; Department of Clinical Biochemistry, Institute of Pediatric Research-Hospital Sant Joan de Déu, Centre for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez Dueñas
authors.affiliation: Center of Molecular Biology-Severo Ochoa, University Autonomous of Madrid-Spanish National Research Council, La Paz Institute for Health Research, Center for Biomedical Research on Rare Diseases, Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Medrano
authors.affiliation: Division of Neonatology, Institute of Pediatric Research-Hospital San Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: García-Alix
authors.affiliation: Department of Pediatric Neurology, Institute of Pediatric Research-Hospital Sant Joan de Déu, Center for Biomedical Research on Rare Diseases, Barcelona, Spain; Department of Clinical Biochemistry, Institute of Pediatric Research-Hospital Sant Joan de Déu, Centre for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
authors.affiliation: Inborn Errors of Metabolism, Biochemical and Molecular Genetics Serv., Biomedical Diagnostic Center, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, Center for Biomedical Research on Rare Diseases, Barcelona, Spain.
authors.forename: Paz
authors.initials: P
authors.lastname: Briones
authors.affiliation: Center of Molecular Biology-Severo Ochoa, University Autonomous of Madrid-Spanish National Research Council, La Paz Institute for Health Research, Center for Biomedical Research on Rare Diseases, Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D001056:Apolipoproteins C / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D018981:Congenital Disorders of Glycosylation / Q000175:diagnosis* / Q000453:epidemiology*; D016208:Databases, Factual; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D012189:Retrospective Studies; D018570:Risk Assessment; D013030:Spain / Q000453:epidemiology
chemical_list: C097349:APOC4 protein, human; D001056:Apolipoproteins C; D005819:Genetic Markers; D000123:Acetyltransferases; C061313:protein N-terminal acetyltransferase
keywords: CDG phenotypes; PMM2-CDG; gene; mutation; rare diseases