Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784573851898740736
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
work_keys_str_mv AT grossialice targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT mianomaurizio targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT lanciottimarina targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT fioreddafrancesca targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT guardodaniela targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT palmisanielena targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT terranovapaola targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT santamariagiuseppe targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT carolifrancesco targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT caorsiroberta targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT volpistefano targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT gattornomarco targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT dufourcarlo targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients
AT ceccheriniisabella targetedngsyieldsplentifulultrararevariantsininbornerrorsofimmunitypatients