Cargando…

Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications

Lysosomal storage diseases (LSDs) are a heterogeneous group of approximately 70 monogenic metabolic disorders whose diagnosis represents an arduous challenge for clinicians due to their variability in phenotype penetrance, clinical manifestations, and high allelic heterogeneity. In recent years, the...

Descripción completa

Detalles Bibliográficos
Autores principales: La Cognata, Valentina, Guarnaccia, Maria, Morello, Giovanna, Ruggieri, Martino, Polizzi, Agata, Cavallaro, Sebastiano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470217/
https://www.ncbi.nlm.nih.gov/pubmed/34576242
http://dx.doi.org/10.3390/ijms221810064
_version_ 1784574142138286080
author La Cognata, Valentina
Guarnaccia, Maria
Morello, Giovanna
Ruggieri, Martino
Polizzi, Agata
Cavallaro, Sebastiano
author_facet La Cognata, Valentina
Guarnaccia, Maria
Morello, Giovanna
Ruggieri, Martino
Polizzi, Agata
Cavallaro, Sebastiano
author_sort La Cognata, Valentina
collection PubMed
description Lysosomal storage diseases (LSDs) are a heterogeneous group of approximately 70 monogenic metabolic disorders whose diagnosis represents an arduous challenge for clinicians due to their variability in phenotype penetrance, clinical manifestations, and high allelic heterogeneity. In recent years, the approval of disease-specific therapies and the rapid emergence of novel rapid diagnostic methods has opened, for a set of selected LSDs, the possibility for inclusion in extensive national newborn screening (NBS) programs. Herein, we evaluated the clinical utility and diagnostic validity of a targeted next-generation sequencing (tNGS) panel (called NBS_LSDs), designed ad hoc to scan the coding regions of six genes (GBA, GAA, SMPD1, IDUA1, GLA, GALC) relevant for a group of LSDs candidate for inclusion in national NBS programs (MPSI, Pompe, Fabry, Krabbe, Niemann Pick A-B and Gaucher diseases). A standard group of 15 samples with previously known genetic mutations was used to test and validate the entire flowchart. Analytical accuracy, sensitivity, and specificity, as well as turnaround time and costs, were assessed. Results showed that the Ion AmpliSeq and Ion Chef System-based high-throughput NBS_LSDs tNGS panel is a fast, accurate, and cost-effective process. The introduction of this technology into routine NBS procedures as a second-tier test along with primary biochemical assays will allow facilitating the identification and management of selected LSDs and reducing diagnostic delay.
format Online
Article
Text
id pubmed-8470217
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84702172021-09-27 Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications La Cognata, Valentina Guarnaccia, Maria Morello, Giovanna Ruggieri, Martino Polizzi, Agata Cavallaro, Sebastiano Int J Mol Sci Article Lysosomal storage diseases (LSDs) are a heterogeneous group of approximately 70 monogenic metabolic disorders whose diagnosis represents an arduous challenge for clinicians due to their variability in phenotype penetrance, clinical manifestations, and high allelic heterogeneity. In recent years, the approval of disease-specific therapies and the rapid emergence of novel rapid diagnostic methods has opened, for a set of selected LSDs, the possibility for inclusion in extensive national newborn screening (NBS) programs. Herein, we evaluated the clinical utility and diagnostic validity of a targeted next-generation sequencing (tNGS) panel (called NBS_LSDs), designed ad hoc to scan the coding regions of six genes (GBA, GAA, SMPD1, IDUA1, GLA, GALC) relevant for a group of LSDs candidate for inclusion in national NBS programs (MPSI, Pompe, Fabry, Krabbe, Niemann Pick A-B and Gaucher diseases). A standard group of 15 samples with previously known genetic mutations was used to test and validate the entire flowchart. Analytical accuracy, sensitivity, and specificity, as well as turnaround time and costs, were assessed. Results showed that the Ion AmpliSeq and Ion Chef System-based high-throughput NBS_LSDs tNGS panel is a fast, accurate, and cost-effective process. The introduction of this technology into routine NBS procedures as a second-tier test along with primary biochemical assays will allow facilitating the identification and management of selected LSDs and reducing diagnostic delay. MDPI 2021-09-17 /pmc/articles/PMC8470217/ /pubmed/34576242 http://dx.doi.org/10.3390/ijms221810064 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
La Cognata, Valentina
Guarnaccia, Maria
Morello, Giovanna
Ruggieri, Martino
Polizzi, Agata
Cavallaro, Sebastiano
Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications
title Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications
title_full Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications
title_fullStr Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications
title_full_unstemmed Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications
title_short Design and Validation of a Custom NGS Panel Targeting a Set of Lysosomal Storage Diseases Candidate for NBS Applications
title_sort design and validation of a custom ngs panel targeting a set of lysosomal storage diseases candidate for nbs applications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470217/
https://www.ncbi.nlm.nih.gov/pubmed/34576242
http://dx.doi.org/10.3390/ijms221810064
work_keys_str_mv AT lacognatavalentina designandvalidationofacustomngspaneltargetingasetoflysosomalstoragediseasescandidatefornbsapplications
AT guarnacciamaria designandvalidationofacustomngspaneltargetingasetoflysosomalstoragediseasescandidatefornbsapplications
AT morellogiovanna designandvalidationofacustomngspaneltargetingasetoflysosomalstoragediseasescandidatefornbsapplications
AT ruggierimartino designandvalidationofacustomngspaneltargetingasetoflysosomalstoragediseasescandidatefornbsapplications
AT polizziagata designandvalidationofacustomngspaneltargetingasetoflysosomalstoragediseasescandidatefornbsapplications
AT cavallarosebastiano designandvalidationofacustomngspaneltargetingasetoflysosomalstoragediseasescandidatefornbsapplications