Cargando…

Next Generation Sequencing Analysis of MODY-X Patients: A Case Report Series

Background: Classic criteria for a maturity-onset diabetes of the young (MODY) diagnosis are often unable to identify all subjects, and traditional Sanger sequencing, using a candidate gene approach, leads to a high prevalence of missed genetic diagnosis, classified as MODY-X. Next generation sequen...

Descripción completa

Detalles Bibliográficos
Autores principales: Maltoni, Giulio, Franceschi, Roberto, Di Natale, Valeria, Al-Qaisi, Randa, Greco, Valentina, Bertorelli, Roberto, De Sanctis, Veronica, Quattrone, Alessandro, Mantovani, Vilma, Cauvin, Vittoria, Zucchini, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605085/
https://www.ncbi.nlm.nih.gov/pubmed/36294752
http://dx.doi.org/10.3390/jpm12101613
_version_ 1784817977893322752
author Maltoni, Giulio
Franceschi, Roberto
Di Natale, Valeria
Al-Qaisi, Randa
Greco, Valentina
Bertorelli, Roberto
De Sanctis, Veronica
Quattrone, Alessandro
Mantovani, Vilma
Cauvin, Vittoria
Zucchini, Stefano
author_facet Maltoni, Giulio
Franceschi, Roberto
Di Natale, Valeria
Al-Qaisi, Randa
Greco, Valentina
Bertorelli, Roberto
De Sanctis, Veronica
Quattrone, Alessandro
Mantovani, Vilma
Cauvin, Vittoria
Zucchini, Stefano
author_sort Maltoni, Giulio
collection PubMed
description Background: Classic criteria for a maturity-onset diabetes of the young (MODY) diagnosis are often unable to identify all subjects, and traditional Sanger sequencing, using a candidate gene approach, leads to a high prevalence of missed genetic diagnosis, classified as MODY-X. Next generation sequencing (NGS) panels provide a highly sensitive method even for rare forms. Methods: We investigated 28 pediatric subjects suspected for MODY-X, utilizing a 15-gene NGS panel for monogenic diabetes (MD). Results: NGS detected variants of uncertain significance (VUS), likely pathogenic or pathogenic for rarer subtypes of MODY, in six patients. We found variants in the wolframin gene (WFS1), traditionally not considered in MD genetic screening panels, in three patients; KCNJ11 gene mutation, typically responsible for neonatal diabetes and rarely causing isolated diabetes in adolescents; INS gene mutation; a variant in the HNF1B gene in a young male with diabetes on sulfonylurea treatment. Conclusion: In our cohort, the availability of an NGS panel for MD was determined for the correct identification of MD subtypes in six patients with MODY-X. Our study underlines how a precise diagnosis utilizing NGS may have an impact on the management of different forms of MODY and, thus, lead to a tailored treatment and enable genetic counselling of other family members.
format Online
Article
Text
id pubmed-9605085
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96050852022-10-27 Next Generation Sequencing Analysis of MODY-X Patients: A Case Report Series Maltoni, Giulio Franceschi, Roberto Di Natale, Valeria Al-Qaisi, Randa Greco, Valentina Bertorelli, Roberto De Sanctis, Veronica Quattrone, Alessandro Mantovani, Vilma Cauvin, Vittoria Zucchini, Stefano J Pers Med Article Background: Classic criteria for a maturity-onset diabetes of the young (MODY) diagnosis are often unable to identify all subjects, and traditional Sanger sequencing, using a candidate gene approach, leads to a high prevalence of missed genetic diagnosis, classified as MODY-X. Next generation sequencing (NGS) panels provide a highly sensitive method even for rare forms. Methods: We investigated 28 pediatric subjects suspected for MODY-X, utilizing a 15-gene NGS panel for monogenic diabetes (MD). Results: NGS detected variants of uncertain significance (VUS), likely pathogenic or pathogenic for rarer subtypes of MODY, in six patients. We found variants in the wolframin gene (WFS1), traditionally not considered in MD genetic screening panels, in three patients; KCNJ11 gene mutation, typically responsible for neonatal diabetes and rarely causing isolated diabetes in adolescents; INS gene mutation; a variant in the HNF1B gene in a young male with diabetes on sulfonylurea treatment. Conclusion: In our cohort, the availability of an NGS panel for MD was determined for the correct identification of MD subtypes in six patients with MODY-X. Our study underlines how a precise diagnosis utilizing NGS may have an impact on the management of different forms of MODY and, thus, lead to a tailored treatment and enable genetic counselling of other family members. MDPI 2022-09-30 /pmc/articles/PMC9605085/ /pubmed/36294752 http://dx.doi.org/10.3390/jpm12101613 Text en © 2022 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
Maltoni, Giulio
Franceschi, Roberto
Di Natale, Valeria
Al-Qaisi, Randa
Greco, Valentina
Bertorelli, Roberto
De Sanctis, Veronica
Quattrone, Alessandro
Mantovani, Vilma
Cauvin, Vittoria
Zucchini, Stefano
Next Generation Sequencing Analysis of MODY-X Patients: A Case Report Series
title Next Generation Sequencing Analysis of MODY-X Patients: A Case Report Series
title_full Next Generation Sequencing Analysis of MODY-X Patients: A Case Report Series
title_fullStr Next Generation Sequencing Analysis of MODY-X Patients: A Case Report Series
title_full_unstemmed Next Generation Sequencing Analysis of MODY-X Patients: A Case Report Series
title_short Next Generation Sequencing Analysis of MODY-X Patients: A Case Report Series
title_sort next generation sequencing analysis of mody-x patients: a case report series
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605085/
https://www.ncbi.nlm.nih.gov/pubmed/36294752
http://dx.doi.org/10.3390/jpm12101613
work_keys_str_mv AT maltonigiulio nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT franceschiroberto nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT dinatalevaleria nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT alqaisiranda nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT grecovalentina nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT bertorelliroberto nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT desanctisveronica nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT quattronealessandro nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT mantovanivilma nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT cauvinvittoria nextgenerationsequencinganalysisofmodyxpatientsacasereportseries
AT zucchinistefano nextgenerationsequencinganalysisofmodyxpatientsacasereportseries