Focusing on Rare Variants Related to Maturity-Onset Diabetes of the Young in Children.

In this study, we analysed the clinical and genetic characteristics and follow-up data of patients with maturity-onset diabetes of the young (MODY). 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. 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 -MODY (36.7%), six with -MODY (20%), five with -MODY (16.7%), five with -MODY (16.7%), two with -MODY (6.7%) and one with -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 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 variant were unable to switch to oral sulfonylurea therapy and continued insulin therapy. Genetic testing is helpful for the precise diagnosis and treatment of patients with MODY, including those with DKA history and positive diabetes autoantibody. -MODY is the most common type of MODY, and patients with variant account for a relatively large proportion of MODY cases in our cohort.