CNR ExploRA

Articolo in rivista, 2023, ENG, 10.3390/biomedicines11071899

Detection of Single-Nucleotide and Copy Number Defects Underlying Hyperphenylalaninemia by Next-Generation Sequencing

Tendi E.A.; Morello G.; Guarnaccia M.;La Cognata V; Petralia S.; Messina M.A.; Meli C.; Fiumara A.; Ruggieri M.; Cavallaro S.;

Istituto per la Ricerca e l'innovazione biomedica - CNR; Dipartimento di Scienze del Farmaco e della Salute, Università di Catania; Centro di Riferimento Regionale per la Cura e il Controllo delle Malattie Metaboliche Congenite dell'Infanzia, Dipartimento di Medicina Clinica e Sperimentale, Policlinico Universitario "Rodolico-San Marco; Unità di Malattie Rare del Sistema Nervoso dell'Infanzia, Sezione di Pediatria e Neuropsichiatria Infantile, Dipartimento di Medicina Clinica e Sperimentale, Policlinico Universitario "Rodolico-San Marco"

Hyperphenylalaninemia (HPA) is the most common inherited amino acid metabolism disorder characterized by serious clinical manifestations, including irreversible brain damage, intel- lectual 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.

Biomedicines