The role of kcnj11 gene in neonatal diabetes / Dina Mohamed Aly Elmaghraby ; Supervised Shereen Mahmoud Shawky , Mona Abdelkader Mohamed Awad , Soha Mahmoud Abdeldayem

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

Background: Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes that occurs in the first 6 months of life. It is a rare disease, occurring in only one in 100,000 to 300,000 live births. Infants with NDM do not produce enough insulin, leading to hyperglycemia. An identified and potentially treatable form of monogenic diabetes is the neonatal diabetes caused by activating mutations of the KCNJ11 gene, which codes for the Kir6.2 subunit of the beta cell of the ATP sensitive potassium channel (KATP). The identification of KCNJ11 mutation has important therapeutic implications, as many patients can replace insulin injections with sulfonylurea tablets. Aim of work: This study aims to identify mutations in the KCNJ11 gene as a cause of permanent NDM in order to identify patients carrying this mutation and modify their treatment regimen. Methods: Sequencing the KCNJ11 gene in 17 Egyptian probands with permanent neonatal diabetes diagnosed with diabetes before the age of 2 years. Results: One case with a previously reported mutation in the KCNJ11 gene (p. R201H) was identified. The patient was successfully shifted from insulin therapy to sulfonylurea. Conclusion: NDM secondary to KCNJ11/Kir6.2 activating mutations has potentially important therapeutic consequences leading to transfering those patients from insulin therapy to sulfonylurea

Issued also as CD