Unlike Western populations where NDM is predominantly due to mutations in the KCNJ11, ABCC8 and INS genes, NDM due to homozygous GCK gene mutations were most prevalent in Oman, having been observed in seven out of 15 NDM patients in whom we established the genetic etiology.
In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified.
Glucokinase (GCK) acts as a glucose sensor and stimulates the release of insulin from pancreatic β-cells and any GCK gene mutations can lead to different forms of diabetes, such as GCK-monogenic diabetes of the young type 2 (MODY2), permanent neonatal diabetes and congenital hyperinsulinism.
To investigate the prevalence and clinical characteristics of heterozygotes of the glucokinase gene mutations G264S and IVS8+2 in the extended pedigree of two patients with permanent neonatal diabetes as a result of glucokinase deficiency (IVS8+2 homozygosity and IVS8+2/G264S compound heterozygosity).