Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations

Abstract

BackgroundNeonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey.Design and methodsNDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed.ResultsTwenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3),ABCC8(n=1) and homozygousINS(n=1). In permanent neonatal diabetes (PNDM) patients, homozygousGCK(n=6),EIF2AK3(n=3),PTF1A(n=3), andINS(n=1) and heterozygousKCNJ11(n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distalPTF1Aenhancer. Both patients with aKCNJ11mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>AINSmutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births.ConclusionsHomozygous mutations inGCK,EIF2AK3and the distal enhancer region ofPTF1Awere the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.