The investigation of genes that known as the cause of mody by a new generation sequence analysis method in children with stress hyperglysemia

Objective and Hypothesis: Determination of MODY genes has ensured that the molecular basis of hyperglycemia is better understood in diabetes subtypes. However, sufficient clinical information regarding whether or not these gene mutations result in susceptibility to stress hyperglycemia is not available in the literature. Stress caused hyperglycemia occurs in some patients while the reason why hyperglycemia does not occur in other children exposing to the same level of stress is not known, and it is supposed that may depend on an underlying genetic effect. This study aims to determine genotype of children with clinical MODY diagnosis by the method of new generation sequence analysis in child patients with detected stress hyperglycemia and to reveal the genetic mutations which create susceptibility to stress hyperglycemia. Method: Child patientswho applied as outpatient to Pediatric clinics or receive treatment as inpatient in Pediatric clinics of this hospital and whose blood glucose has been measured above 150 mg/dl at least one time, not have a known DM diagnosis, and in the age range between 28 days and 18 years old. Demographic characteristics of patients with detected stress hyperglycemia, DM history of their family, weight-height, full urine analysis, blood gas values, primer diagnosis, treatments received before increased blood glucose is detected, period of reduction of blood glucose to normal levels have been recorded in the case report and blood samples of the patients have been examined with the new generation sequence analysis method. The gene mutations known as the reason of MODY such as HNF4A, HNF1A, HNF1B, GCK, CEL, PAX, İPF1, KLF11, NEUROD1, İNS, BLK, ABCC8, KCNJ11have been screened and recorded in the case report. Evidences: 51 patients in total including 33 (64.7%) male and 18 (35.3%) female have been included in the study. The median age of the patients is 44 months (between 5 and 204 months). Mutation has been detected in 43.1% of patients. 11 patients with detected polymorphism (21.6%), 8 patients whose clinical significance has been detected as uncertain (15.7%) and 3 events on whom disease based variances have been detected (5.9%) are established. Three new missense mutations have been detected including F621C in HNF1A gene of 1 patient, L461F in ABCC8 gene of 1 patient and V597I. The primer diagnoses were Wilms TM, pneumonia+growth deficiency retarded development+malnutrition.