Genotype-Phenotypecorrelation Of K(Atp)Channel Gene Defects Causing Permanent Neonatal Diabetes In Indian Patients

Background There are very few reports pertaining to Indian patients with neonatal diabetes mellitus (NDM). Activating or gain of function mutations of K(ATP)channel genes namelyKCNJ11andABCC8are most predominant cause of permanent neonatal diabetes mellitus (PNDM). Objectives To identify the genotype-phenotype correlation of K(ATP)channel gene defects in a large series of (n = 181) Indian PNDM patients. Methods Direct sequencing of all exons ofKCNJ11andABCC8genes in all 181 patients with PNDM were performed. Clinical and biochemical data were collected. Results We have identified the molecular basis of K-ATP-NDM in 39 out of 181 patients (22%). Of these, 20 hadKCNJ11mutations and 19 hadABCC8mutations, thus comprising 51% ofKCNJ11and 49% ofABCC8. There were four novel mutations (D1128Tfs*16, Y1287C, S1422T, and H1537R) inABCC8gene. Three patients withKCNJ11mutations had developmental delay with DEND syndrome. In patients withABCC8mutations developmental delay was seen in seven out of 19 (36.8%). Of this, three patients (15.7%) had DEND phenotype and four (21%) had iDEND. Of the 39 patients, 33 (84%) patients were shifted to sulfonylurea therapy (glibenclamide). Of this, 19(57.5%) patients harboredKCNJ11mutations and 14(42.1%)ABCC8mutations. Conclusions This is the first largest study in NDM patients in India demonstrating the importance of K(ATP)channel gene mutation screening in PNDM and efficacy of glibenclamide for Indian patients with K-ATP-PNDM. The success rate of transfer is more in patients withKCNJ11mutations compared with those withABCC8mutations.