title: Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism.
abstract: BACKGROUND
  Next-generation sequencing (NGS) technology has allowed the promotion of genetic diagnosis and are becoming increasingly inexpensive and faster. To evaluate the utility of NGS in the clinical field, a targeted genetic panel approach was designed for the diagnosis of a set of inborn errors of metabolism (IEM). The final aim of the study was to compare the findings for the diagnostic yield of NGS in patients who presented with consistent clinical and biochemical suspicion of IEM with those obtained for patients who did not have specific biomarkers.
  
  
  METHODS
  The subjects studied (n = 146) were classified into two categories: Group 1 (n = 81), which consisted of patients with clinical and biochemical suspicion of IEM, and Group 2 (n = 65), which consisted of IEM cases with clinical suspicion and unspecific biomarkers. A total of 171 genes were analyzed using a custom targeted panel of genes followed by Sanger validation.
  
  
  RESULTS
  Genetic diagnosis was achieved in 50% of patients (73/146). In addition, the diagnostic yield obtained for Group 1 was 78% (63/81), and this rate decreased to 15.4% (10/65) in Group 2 (X2 = 76.171; p < 0.0001).
  
  
  CONCLUSIONS
  A rapid and effective genetic diagnosis was achieved in our cohort, particularly the group that had both clinical and biochemical indications for the diagnosis.
authors.affiliation: Department of Clinical Biochemistry and Institut d'Investigació Sanitària Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: Dèlia
authors.initials: D
authors.lastname: Yubero
authors.affiliation: Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.|Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Brandi
authors.affiliation: Department of Clinical Biochemistry and Institut d'Investigació Sanitària Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Ormazabal
authors.affiliation: Department of Neurology, Hospital Sant Joan de Déu, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Àngels
authors.initials: À
authors.lastname: Garcia-Cazorla
authors.affiliation: Department of Neurology, Hospital Sant Joan de Déu, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez-Dueñas
authors.affiliation: Department of Neurology, Hospital Sant Joan de Déu, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Campistol
authors.affiliation: Institut de Bioquímica Clínica, Hospital Clínic i Provincial, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
authors.affiliation: Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Palau
authors.affiliation: Department of Clinical Biochemistry and Institut d'Investigació Sanitària Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
authors.affiliation: Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Armstrong
mesh_terms: D004252:DNA Mutational Analysis; D005819:Genetic Markers; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation
chemical_list: D005819:Genetic Markers