Detection of Single-Nucleotide and Copy Number Defects Underlying Hyperphenylalaninemia by Next-Generation Sequencing
Elisabetta Anna Tendi,
Giovanna Morello,
Maria Guarnaccia,
Valentina La Cognata,
Salvatore Petralia,
Maria Anna Messina,
Concetta Meli,
Agata Fiumara,
Martino Ruggieri,
Sebastiano Cavallaro
Affiliations
Elisabetta Anna Tendi
Biomedical Sciences Department, Institute for Biomedical Research and Innovation, National Research Council, Via Paolo Gaifami 18, 95026 Catania, Italy
Giovanna Morello
Biomedical Sciences Department, Institute for Biomedical Research and Innovation, National Research Council, Via Paolo Gaifami 18, 95026 Catania, Italy
Maria Guarnaccia
Biomedical Sciences Department, Institute for Biomedical Research and Innovation, National Research Council, Via Paolo Gaifami 18, 95026 Catania, Italy
Valentina La Cognata
Biomedical Sciences Department, Institute for Biomedical Research and Innovation, National Research Council, Via Paolo Gaifami 18, 95026 Catania, Italy
Salvatore Petralia
Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy
Maria Anna Messina
Regional Reference Center for the Treatment and Control of Congenital Metabolic Diseases of Childhood, Department of Clinical and Experimental Medicine, University Hospital Policlinico “Rodolico-San Marco”, 95123 Catania, Italy
Concetta Meli
Regional Reference Center for the Treatment and Control of Congenital Metabolic Diseases of Childhood, Department of Clinical and Experimental Medicine, University Hospital Policlinico “Rodolico-San Marco”, 95123 Catania, Italy
Agata Fiumara
Regional Reference Center for the Treatment and Control of Congenital Metabolic Diseases of Childhood, Department of Clinical and Experimental Medicine, University Hospital Policlinico “Rodolico-San Marco”, 95123 Catania, Italy
Martino Ruggieri
Unit of Rare Diseases of the Nervous System in Childhood, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University Hospital Policlinico “Rodolico-San Marco”, 95123 Catania, Italy
Sebastiano Cavallaro
Biomedical Sciences Department, Institute for Biomedical Research and Innovation, National Research Council, Via Paolo Gaifami 18, 95026 Catania, Italy
Hyperphenylalaninemia (HPA) is the most common inherited amino acid metabolism disorder characterized by serious clinical manifestations, including irreversible brain damage, intellectual deficiency and epilepsy. Due to its extensive genic and allelic heterogeneity, next-generation sequencing (NGS) technology may help to identify the molecular basis of this genetic disease. Herein, we describe the development and validation of a targeted NGS (tNGS) approach for the simultaneous detection of single-nucleotide changes and copy number variations (CNVs) in genes associated with HPA (PAH, GCH1, PTS, QDPR, PCBD1, DNAJC12) or useful for its differential diagnosis (SPR). Our tNGS approach offers the possibility to detail, with a high accuracy and in a single workflow, the combined effect of a broader spectrum of genomic variants in a comprehensive view, providing a significant step forward in the development of optimized patient care and management.
