Abstract
BACKGROUND: Single gene variants that give rise to neonatal diabetes mellitus (NDM), maturity onset diabetes of the young (MODY), and syndromic forms of diabetes mellitus (SDM) are responsible for 3.1% to 4.2% of all diabetes cases. This single-center study with a relatively larger sample size aimed to evaluate the clinical and genetic characteristics of Chinese children with suspected monogenic diabetes (MD) using next-generation sequencing (NGS) methods. MATERIALS AND METHODS: Data were collected from 1550 consecutive children diagnosed with diabetes/hyperglycemia at the Endocrinology Department of Children's Hospital of Nanjing Medical University from 2012 to 2023. The genotype and phenotype of 138 children with suspected MD were retrospectively analyzed. RESULTS: Among 138 children, 16, 97, and 25 patients with NDM, suspected MODY, and SDM, respectively, were assessed by NGS, with a pick-up rate of 87.5%, 57.8%, and 56%, respectively. In total, there was a high pick-up rate of MD, with 58% (80 of 138) among antibody-negative pediatric patients. Pathogenic variants were found in GCK, HNF1A, INS, KCNJ11, INSR, HNF4A, ABCC8, WFS1, ALMS1, HNF1B, BLK, and ZFP57 genes with 13 novel variants in addition to 4 patients with copy number variants. In this cohort, GCK-MODY was the leading cause and the mildest type of MODY. GCK-MODY displayed favorable lipid profile when compared to non-GCK-MODY and MODYX, which might be cardioprotective. Following an accurate genetic diagnosis of diabetes, 19 patients switched from insulin therapy to oral agents or lifestyle interventions. CONCLUSION: NGS tests helped to identify the precise etiology of monogenic diabetic patients, which has implications for better individualized management.