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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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 |
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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 |
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