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The aim of this study is to elucidate the aetiology and clinical features of neonatal and early-onset diabetes in a large database for paediatric diabetes patients in Ukraine.We established a Pediatric Diabetes Register to identify patients diagnosed with diabetes before 9 months of age. Genetic testing was undertaken for 66 patients from 65 unrelated families with diabetes diagnosed within the first 6 months of life (neonatal diabetes, n=36) or between 6 and 9 months (early-onset diabetes, n=30).We determined the genetic etiology in 86.1% of patients (31/36) diagnosed before 6 months and in 20% (6/30) diagnosed between 6 and 9 months. Fourteen individuals (37.8% of those with a genetic cause identified) had activating heterozygous variants in ABCC8 or KCNJ11. An additional ten individuals had pathogenic variants in the INS or GCK genes, whilst 4 had 6q24 transient neonatal diabetes. Rare genetic subtypes (including pathogenic variants in EIF2AK3, GLIS3, INSR, PDX1, LRBA, RFX6 and FOXP3) were identified in nine probands (24.3% of solved cases), 6 of whom died. In total, 8 individuals died between infancy and childhood, all of them were diagnosed before 6 months and had received a genetic diagnosis.In the last decade, the increased availability of comprehensive genetic testing has resulted in increased recognition of the contribution of rare genetic subtypes within pediatric diabetes cohorts. In our study, we identified a high mortality rate among these patients. |
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