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Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients
Inborn errors of immunity (IEI) include a large group of inherited diseases sharing either poor, dysregulated, or absent and/or acquired function in one or more components of the immune system. Next-generation sequencing (NGS) has driven a rapid increase in the recognition of such defects, though th...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469131/ https://www.ncbi.nlm.nih.gov/pubmed/34573280 http://dx.doi.org/10.3390/genes12091299 |
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author | Grossi, Alice Miano, Maurizio Lanciotti, Marina Fioredda, Francesca Guardo, Daniela Palmisani, Elena Terranova, Paola Santamaria, Giuseppe Caroli, Francesco Caorsi, Roberta Volpi, Stefano Gattorno, Marco Dufour, Carlo Ceccherini, Isabella |
author_facet | Grossi, Alice Miano, Maurizio Lanciotti, Marina Fioredda, Francesca Guardo, Daniela Palmisani, Elena Terranova, Paola Santamaria, Giuseppe Caroli, Francesco Caorsi, Roberta Volpi, Stefano Gattorno, Marco Dufour, Carlo Ceccherini, Isabella |
author_sort | Grossi, Alice |
collection | PubMed |
description | Inborn errors of immunity (IEI) include a large group of inherited diseases sharing either poor, dysregulated, or absent and/or acquired function in one or more components of the immune system. Next-generation sequencing (NGS) has driven a rapid increase in the recognition of such defects, though the wide heterogeneity of genetically diverse but phenotypically overlapping diseases has often prevented the molecular characterization of the most complex patients. Two hundred and seventy-two patients were submitted to three successive NGS-based gene panels composed of 58, 146, and 312 genes. Along with pathogenic and likely pathogenic causative gene variants, accounting for the corresponding disorders (37/272 patients, 13.6%), a number of either rare (probably) damaging variants in genes unrelated to patients’ phenotype, variants of unknown significance (VUS) in genes consistent with their clinics, or apparently inconsistent benign, likely benign, or VUS variants were also detected. Finally, a remarkable amount of yet unreported variants of unknown significance were also found, often recurring in our dataset. The NGS approach demonstrated an expected IEI diagnostic rate. However, defining the appropriate list of genes for these panels may not be straightforward, and the application of unbiased approaches should be taken into consideration, especially when patients show atypical clinical pictures. |
format | Online Article Text |
id | pubmed-8469131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84691312021-09-27 Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients Grossi, Alice Miano, Maurizio Lanciotti, Marina Fioredda, Francesca Guardo, Daniela Palmisani, Elena Terranova, Paola Santamaria, Giuseppe Caroli, Francesco Caorsi, Roberta Volpi, Stefano Gattorno, Marco Dufour, Carlo Ceccherini, Isabella Genes (Basel) Article Inborn errors of immunity (IEI) include a large group of inherited diseases sharing either poor, dysregulated, or absent and/or acquired function in one or more components of the immune system. Next-generation sequencing (NGS) has driven a rapid increase in the recognition of such defects, though the wide heterogeneity of genetically diverse but phenotypically overlapping diseases has often prevented the molecular characterization of the most complex patients. Two hundred and seventy-two patients were submitted to three successive NGS-based gene panels composed of 58, 146, and 312 genes. Along with pathogenic and likely pathogenic causative gene variants, accounting for the corresponding disorders (37/272 patients, 13.6%), a number of either rare (probably) damaging variants in genes unrelated to patients’ phenotype, variants of unknown significance (VUS) in genes consistent with their clinics, or apparently inconsistent benign, likely benign, or VUS variants were also detected. Finally, a remarkable amount of yet unreported variants of unknown significance were also found, often recurring in our dataset. The NGS approach demonstrated an expected IEI diagnostic rate. However, defining the appropriate list of genes for these panels may not be straightforward, and the application of unbiased approaches should be taken into consideration, especially when patients show atypical clinical pictures. MDPI 2021-08-24 /pmc/articles/PMC8469131/ /pubmed/34573280 http://dx.doi.org/10.3390/genes12091299 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 Grossi, Alice Miano, Maurizio Lanciotti, Marina Fioredda, Francesca Guardo, Daniela Palmisani, Elena Terranova, Paola Santamaria, Giuseppe Caroli, Francesco Caorsi, Roberta Volpi, Stefano Gattorno, Marco Dufour, Carlo Ceccherini, Isabella Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients |
title | Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients |
title_full | Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients |
title_fullStr | Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients |
title_full_unstemmed | Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients |
title_short | Targeted NGS Yields Plentiful Ultra-Rare Variants in Inborn Errors of Immunity Patients |
title_sort | targeted ngs yields plentiful ultra-rare variants in inborn errors of immunity patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469131/ https://www.ncbi.nlm.nih.gov/pubmed/34573280 http://dx.doi.org/10.3390/genes12091299 |
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