biostudies-literatureUnknown2025Ding Y<b>Background:</b> In this study, we analysed the clinical and genetic characteristics and follow-up data of patients with maturity-onset diabetes of the young (MODY). <b>Methods:</b> From January 2015 to December 2022, patients with persistent hyperglycaemia suspected of having monogenic diabetes or diabetes syndrome were recruited, and next-generation sequencing (NGS) was performed at the Shanghai Children's Medical Center. Patients' clinical and laboratory findings were recorded preceding follow-ups. Candidate variants were verified using Sanger sequencing. Variant pathogenicity was evaluated according to the American College of Medical Genetics and Genomics (ACMG) guidelines. <b>Results:</b> Genetic testing was performed in 175 children. MODY-related pathogenic or likely pathogenic gene variants were identified in 30 patients from different families. Of these, 11 were diagnosed with <i>GCK</i>-MODY (36.7%), six with <i>INS</i>-MODY (20%), five with <i>HNF1A</i>-MODY (16.7%), five with <i>ABCC8</i>-MODY (16.7%), two with <i>HNF1B</i>-MODY (6.7%) and one with <i>HNF4A</i>-MODY (3.3%). There was one shift variant and seven splice-site variants, and the rest were missense variants. We discovered six novel variants. Of the 30 patients, 63.3% had a family history of diabetes, 13.3% had diabetic ketoacidosis (DKA), and 16.7% had positive diabetes-associated autoantibodies. The diabetes phenotype of patients with the <i>INS</i> variant was similar to that of patients with type 1 diabetes. All patients, including those having positive autoantibodies, required long-term insulin therapy during follow-ups. Four patients with the <i>ABCC8</i> variant were unable to switch to oral sulfonylurea therapy and continued insulin therapy. <b>Conclusion:</b> Genetic testing is helpful for the precise diagnosis and treatment of patients with MODY, including those with DKA history and positive diabetes autoantibody. <i>GCK</i>-MODY is the most common type of MODY, and patients with <i>INS</i> variant account for a relatively large proportion of MODY cases in our cohort.Pediatric diabetes8155443https://www.ebi.ac.uk/biostudies/studies/S-EPMC12017003biostudies-literatureFocusing on Rare Variants Related to Maturity-Onset Diabetes of the Young in Children.PMC12017003Li JYao REZhang QWang LLi NLi XDing YLou DChen YYu TWang XWang YGao SChang GfalseFocusing on Rare Variants Related to Maturity-Onset Diabetes of the Young in Children.<b>Background:</b> In this study, we analysed the clinical and genetic characteristics and follow-up data of patients with maturity-onset diabetes of the young (MODY). <b>Methods:</b> From January 2015 to December 2022, patients with persistent hyperglycaemia suspected of having monogenic diabetes or diabetes syndrome were recruited, and next-generation sequencing (NGS) was performed at the Shanghai Children's Medical Center. Patients' clinical and laboratory findings were recorded preceding follow-ups. Candidate variants were verified using Sanger sequencing. Variant pathogenicity was evaluated according to the American College of Medical Genetics and Genomics (ACMG) guidelines. <b>Results:</b> Genetic testing was performed in 175 children. MODY-related pathogenic or likely pathogenic gene variants were identified in 30 patients from different families. Of these, 11 were diagnosed with <i>GCK</i>-MODY (36.7%), six with <i>INS</i>-MODY (20%), five with <i>HNF1A</i>-MODY (16.7%), five with <i>ABCC8</i>-MODY (16.7%), two with <i>HNF1B</i>-MODY (6.7%) and one with <i>HNF4A</i>-MODY (3.3%). There was one shift variant and seven splice-site variants, and the rest were missense variants. We discovered six novel variants. Of the 30 patients, 63.3% had a family history of diabetes, 13.3% had diabetic ketoacidosis (DKA), and 16.7% had positive diabetes-associated autoantibodies. The diabetes phenotype of patients with the <i>INS</i> variant was similar to that of patients with type 1 diabetes. All patients, including those having positive autoantibodies, required long-term insulin therapy during follow-ups. Four patients with the <i>ABCC8</i> variant were unable to switch to oral sulfonylurea therapy and continued insulin therapy. <b>Conclusion:</b> Genetic testing is helpful for the precise diagnosis and treatment of patients with MODY, including those with DKA history and positive diabetes autoantibody. <i>GCK</i>-MODY is the most common type of MODY, and patients with <i>INS</i> variant account for a relatively large proportion of MODY cases in our cohort.2025-01-01T00:00:00Z20252026-06-06T16:49:20.289Z2025-07-04T03:05:51.093ZS-EPMC120170034030394410.1155/pedi/8155443