title: Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing.
abstract: Glycogen storage disease (GSD) is an umbrella term for a group of genetic disorders that involve the abnormal metabolism of glycogen; to date, 23 types of GSD have been identified. The nonspecific clinical presentation of GSD and the lack of specific biomarkers mean that Sanger sequencing is now widely relied on for making a diagnosis. However, this gene-by-gene sequencing technique is both laborious and costly, which is a consequence of the number of genes to be sequenced and the large size of some genes.
  
  
  
  This work reports the use of massive parallel sequencing to diagnose patients at our laboratory in Spain using either a customized gene panel (targeted exome sequencing) or the Illumina Clinical-Exome TruSight One Gene Panel (clinical exome sequencing (CES)). Sequence variants were matched against biochemical and clinical hallmarks.
  
  
  
  Pathogenic mutations were detected in 23 patients. Twenty-two mutations were recognized (mostly loss-of-function mutations), including 11 that were novel in GSD-associated genes. In addition, CES detected five patients with mutations in ALDOB, LIPA, NKX2-5, CPT2, or ANO5. Although these genes are not involved in GSD, they are associated with overlapping phenotypic characteristics such as hepatic, muscular, and cardiac dysfunction.
  
  
  
  These results show that next-generation sequencing, in combination with the detection of biochemical and clinical hallmarks, provides an accurate, high-throughput means of making genetic diagnoses of GSD and related diseases.Genet Med 18 10, 1037-1043.
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Instituto de Investigación La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Vega
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Instituto de Investigación La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Medrano
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Instituto de Investigación La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Navarrete
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Instituto de Investigación La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Lourdes R
authors.initials: LR
authors.lastname: Desviat
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Instituto de Investigación La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Merinero
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Instituto de Investigación La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Rodríguez-Pombo
authors.affiliation: Unidad de Nutrición y Metabolopatías, Hospital La Fe, Valencia, Spain.
authors.forename: Isidro
authors.identifier: 0000-0003-4450-1213
authors.initials: I
authors.lastname: Vitoria
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Instituto de Investigación La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ugarte
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Instituto de Investigación La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Pérez-Cerdá
authors.affiliation: Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.|Instituto de Investigación La Paz (IdiPAZ), Madrid, Spain.
authors.forename: Belen
authors.initials: B
authors.lastname: Pérez
mesh_terms: D000293:Adolescent; D000328:Adult; D000075368:Anoctamins; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics; D059472:Exome / Q000235:genetics; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics; D006003:Glycogen / Q000235:genetics* / Q000378:metabolism; D006008:Glycogen Storage Disease / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D057089:Pathology, Molecular; D002787:Sterol Esterase / Q000235:genetics; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: C547813:ANO5 protein, human; D000075368:Anoctamins; D018118:Chloride Channels; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D006003:Glycogen; C503451:LIPA protein, human; D002787:Sterol Esterase; D005634:Fructose-Bisphosphate Aldolase