{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:51:45Z","timestamp":1760147505461,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>In pediatric diabetology, a precise diagnosis is very important because it allows early and correct clinical management of the patient. Monogenic diabetes (MD), which accounts for 1\u20136% of all pediatric\u2013adolescent diabetes cases, is the most relevant example of precision medicine. The definitive diagnosis of MD, possible only by genetic testing, allows us to direct patients to more appropriate therapy in relation to the identified mutation. In some cases, MD patients can avoid insulin and be treated with oral hypoglycemic drugs with a perceptible impact on both the quality of life and the healthcare costs. However, the genetic and phenotypic heterogeneity of MD and the overlapping clinical characteristics between different forms, can complicate the diagnostic process. In recent years, the development of Next-Generation Sequencing (NGS) methodology, which allows the simultaneous analysis of multiple genes, has revolutionized molecular diagnostics, becoming the cornerstone of MD precision diagnosis. We report two cases of patients with clinical suspects of MD in which a genetic test was carried out, using a NGS multigenic panel, and it clarified the correct pathogenesis of diabetes, allowing us to better manage the disease both in probands and other affected family members.<\/jats:p>","DOI":"10.3390\/medicina59020310","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T03:01:45Z","timestamp":1675825305000},"page":"310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Pathogenic Diagnosis in Pediatric Diabetology: Next Generation Sequencing and Precision Therapy"],"prefix":"10.3390","volume":"59","author":[{"given":"Giovanna","family":"Maione","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, Via S. Pansini, 5-80131 Naples, Italy"},{"name":"CEINGE Advanced Biotechnology, Via G. Salvatore, 486-80145 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Iafusco","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, Via S. Pansini, 5-80131 Naples, Italy"},{"name":"CEINGE Advanced Biotechnology, Via G. Salvatore, 486-80145 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Zanfardino","sequence":"additional","affiliation":[{"name":"Regional Centre of Paediatric Diabetology \u201cG. Stoppoloni\u201d, Department of Woman, Child and of General and Specialized Surgery, University of Campania \u201cL. Vanvitelli\u201d, Via L. De Crecchio, 2-80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Piscopo","sequence":"additional","affiliation":[{"name":"Regional Centre of Paediatric Diabetology \u201cG. Stoppoloni\u201d, Department of Woman, Child and of General and Specialized Surgery, University of Campania \u201cL. Vanvitelli\u201d, Via L. De Crecchio, 2-80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9049-2875","authenticated-orcid":false,"given":"Gulsum","family":"Ozen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Health Science, Kecioren Training and Research Hospital, Ankara 06100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dario","family":"Iafusco","sequence":"additional","affiliation":[{"name":"Regional Centre of Paediatric Diabetology \u201cG. Stoppoloni\u201d, Department of Woman, Child and of General and Specialized Surgery, University of Campania \u201cL. Vanvitelli\u201d, Via L. De Crecchio, 2-80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1070-4231","authenticated-orcid":false,"given":"Nadia","family":"Tinto","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, Via S. Pansini, 5-80131 Naples, Italy"},{"name":"CEINGE Advanced Biotechnology, Via G. Salvatore, 486-80145 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.23736\/S0026-4946.20.05838-7","article-title":"Congenital Diabetes Mellitus","volume":"72","author":"Iafusco","year":"2020","journal-title":"Minerva Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1007\/s00592-018-1198-8","article-title":"Glucokinase Deficit and Birthweight: Does Maternal Hyperglycemia Always Meet Fetal Needs?","volume":"55","author":"Bitterman","year":"2018","journal-title":"Acta Diabetol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1210\/jc.2016-2490","article-title":"Monogenic Diabetes Accounts for 6.3% of Cases Referred to 15 Italian Pediatric Diabetes Centers During 2007 to 2012","volume":"102","author":"Delvecchio","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Donath, X., Saint-Martin, C., Dubois-Laforgue, D., Rajasingham, R., Mifsud, F., Ciangura, C., Timsit, J., Bellann\u00e9-Chantelot, C., and Monogenic Diabetes Study Group of the Soci\u00e9t\u00e9 Francophone du Diab\u00e8te (2019). Next-Generation Sequencing Identifies Monogenic Diabetes in 16% of Patients with Late Adolescence\/Adult-Onset Diabetes Selected on a Clinical Basis: A Cross-Sectional Analysis. BMC Med., 17.","DOI":"10.1186\/s12916-019-1363-0"},{"key":"ref_5","unstructured":"(2022, February 08). Maturity-Onset Diabetes of the Young (MODY): How Many Cases Are We Missing?\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/20499044\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/pedi.12732","article-title":"ISPAD Clinical Practice Consensus Guidelines 2018: Management of Cystic Fibrosis-Related Diabetes in Children and Adolescents","volume":"19","author":"Moran","year":"2018","journal-title":"Pediatr. Diabetes"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Iafusco, F., Maione, G., Mazzaccara, C., Di Candia, F., Mozzillo, E., Franzese, A., and Tinto, N. (2021). NGS Analysis Revealed Digenic Heterozygous GCK and HNF1A Variants in a Child with Mild Hyperglycemia: A Case Report. Diagnostics, 11.","DOI":"10.3390\/diagnostics11071164"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.2337\/dc10-0561","article-title":"Double Heterozygous Mutations Involving Both HNF1A\/MODY3 and HNF4A\/MODY1 Genes: A Case Report","volume":"33","author":"Forlani","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"on behalf of the ACMG Laboratory Quality Assurance Committee, Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W.W., Hegde, M., and Lyon, E. (2015). Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med., 17, 405\u2013423.","DOI":"10.1038\/gim.2015.30"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1093\/ndt\/gfh348","article-title":"Renal Cysts and Diabetes Syndrome Resulting from Mutations in Hepatocyte Nuclear Factor-1beta","volume":"19","author":"Bingham","year":"2004","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Barretta, F., Mirra, B., Monda, E., Caiazza, M., Lombardo, B., Tinto, N., Scudiero, O., Frisso, G., and Mazzaccara, C. (2020). The Hidden Fragility in the Heart of the Athletes: A Review of Genetic Biomarkers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186682"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s00125-017-4226-2","article-title":"Precision Diabetes: Learning from Monogenic Diabetes","volume":"60","author":"Hattersley","year":"2017","journal-title":"Diabetologia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109154","DOI":"10.1016\/j.diabres.2021.109154","article-title":"Next- Generation Sequencing Is an Effective Method for Diagnosing Patients with Different Forms of Monogenic Diabetes","volume":"183","author":"Jakiel","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00592-020-01641-2","article-title":"Prenatal Diagnosis of HNF1b Mutation Allows Recognition of Neonatal Dysglycemia","volume":"58","author":"Iafusco","year":"2021","journal-title":"Acta Diabetol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.2337\/dci20-0065","article-title":"Monogenic Diabetes: From Genetic Insights to Population-Based Precision in Care. Reflections From a Diabetes Care Editors\u2019 Expert Forum","volume":"43","author":"Riddle","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1007\/s13300-020-00864-4","article-title":"Treatment Options for MODY Patients: A Systematic Review of Literature","volume":"11","author":"Delvecchio","year":"2020","journal-title":"Diabetes Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e306","DOI":"10.1515\/cclm-2019-0137","article-title":"Molecular Diagnosis of MODY3 Permitted to Reveal a de Novo 12q24.31 Deletion and to Explain a Complex Phenotype in a Young Diabetic Patient","volume":"57","author":"Iafusco","year":"2019","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s00592-018-1179-y","article-title":"Can HbA1c Combined with Fasting Plasma Glucose Help to Assess Priority for GCK-MODY vs HNF1A-MODY Genetic Testing?","volume":"55","author":"Delvecchio","year":"2018","journal-title":"Acta Diabetol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1007\/s001250051531","article-title":"MODY 2 Presenting as Neonatal Hyperglycaemia: A Need to Reshape the Definition of \u201cNeonatal Diabetes\u201d?","volume":"43","author":"Prisco","year":"2000","journal-title":"Diabetologia"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Capuano, M., Garcia-Herrero, C.M., Tinto, N., Carluccio, C., Capobianco, V., Coto, I., Cola, A., Iafusco, D., Franzese, A., and Zagari, A. (2012). Glucokinase (GCK) Mutations and Their Characterization in MODY2 Children of Southern Italy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038906"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tinto, N., Zagari, A., Capuano, M., De Simone, A., Capobianco, V., Daniele, G., Giugliano, M., Spadaro, R., Franzese, A., and Sacchetti, L. (2008). Glucokinase Gene Mutations: Structural and Genotype-Phenotype Analyses in MODY Children from South Italy. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001870"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pinelli, M., Acquaviva, F., Barbetti, F., Caredda, E., Cocozza, S., Delvecchio, M., Mozzillo, E., Pirozzi, D., Prisco, F., and Rabbone, I. (2013). Identification of Candidate Children for Maturity-Onset Diabetes of the Young Type 2 (MODY2) Gene Testing: A Seven-Item Clinical Flowchart (7-IF). PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079933"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.1399-5448.2011.00788.x","article-title":"Onset of Type 1 Diabetes Mellitus in Two Patients with Maturity Onset Diabetes of the Young","volume":"13","author":"Maltoni","year":"2012","journal-title":"Pediatr. Diabetes"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/2\/310\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:27:36Z","timestamp":1760120856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/2\/310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,8]]},"references-count":23,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["medicina59020310"],"URL":"https:\/\/doi.org\/10.3390\/medicina59020310","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2023,2,8]]}}}