Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes resulting from mutations in a number of different genes encoding proteins that play a key role in the normal function of the pancreatic beta-cell. Mutations in the genes encoding the ATP-sensitive potassium channel [(potassium inwardly rectifying channel, subfamily J, member11 (KCNJ11) and ATP-binding cassette transporter subfamily C, member 8 (ABCC8)] and the insulin (INS) genes are the commonest causes of the NDM. The identification of these mutations by genetic test»ing is critical for appropriate management and to guide genetic counseling. This study aimed to determine ABCC8 and IN genes mutations in a group of Egyptian diabetic neonates and infants under the age of 1 year and to determine other candidate genetic causes of NDM according to the patient{u2019}s clinical phenotype. DNA sequencing of the coding regions and intronic boundaries of ABCC8 and INS genes was done in 25 patients. Further candidate genes sequencing according to the clinical phenotype was done. Two patients (10%) had three ABCC8 mutations in the form of a compound heterozygous (p.N131K/p.R598*) in one patient and a homozygous (p.R1554Q) in the other patient

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