Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism

• Published in: PloS one Vol. 11; no. 5; p. e0156359
• Main Authors: Yubero, Dèlia, Brandi, Núria, Ormazabal, Aida, Garcia-Cazorla, Àngels, Pérez-Dueñas, Belén, Campistol, Jaime, Ribes, Antonia, Palau, Francesc, Artuch, Rafael, Armstrong, Judith
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.05.2016; Public Library of Science (PLoS)
• Subjects: ADN; Amino acids; Analysis; Biochemistry; Biology and Life Sciences; Biomarkers; Care and treatment; Defects; Development and progression; Diagnosis; Diagnostic systems; DNA; DNA Mutational Analysis; DNA sequencing; Enzymes; Gene sequencing; Genes; Genetic aspects; Genetic diseases; Genetic disorders; Genetic Markers; Genetic screening; Genetics; Genotypes; Genètica mèdica; High-Throughput Nucleotide Sequencing - methods; Humans; Identification and classification; Inborn errors of metabolism; Innovations; Laboratories; Malalties hereditàries; Medical diagnosis; Medical genetics; Medicine and Health Sciences; Metabolism; Metabolism, Inborn Errors - classification; Metabolism, Inborn Errors - diagnosis; Metabolism, Inborn Errors - genetics; Metabolisme; Metabolites; Methods; Molecular targeted therapy; Mutació (Biologia); Mutation; Mutation (Biology); Neurology; Patients; Research and analysis methods; Singers; Studies; Working groups; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0156359

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. 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. 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). A rapid and effective genetic diagnosis was achieved in our cohort, particularly the group that had both clinical and biochemical indications for the diagnosis.