New insights from Neonatal Diabetes. (360G-Wellcome-098395_Z_12_Z)

Neonatal diabetes is a rare monogenic subtype of diabetes that is diagnosed before 6 months. Our team has shown that mutations in the Kir6.2 and SUR1 subunits of the beta-cell potassium (KATP) channel are the commonest cause of neonatal diabetes. We established that 90% of KATP patients despite being insulin dependent could replace their insulin injections with sulphonylurea tablets and improve glycaemic control. These findings mean that genetic testing at diagnosis of neonatal diabetes is cruc ial for appropriate treatment. Consequently we have analysed samples from over 920 patients from 71 countries. We have identified 8 novel genetic causes of neonatal diabetes and by clinical and physiological study in these experiments of nature made novel observations of the physiology of human beta-cells. The aim of this programme is to investigate the function and development of the human pancreatic beta-cell by genetic, functional, physiological and clinical studies of patients with neona tal diabetes. We will offer a rapid, comprehensive, international genetic testing service adding state of the art next sequencing technology to our diagnostic pipeline. Patients with a mutation in a known gene will be studied to understand normal and pathological beta-cell pathways in man. Patients in whom mutations in the 20 known genes have been excluded (c.35% cases) we will use linkage (were appropriate) combined with exome/genome sequencing to discover novel genes and novel regulatory regions. Functional and physiological studies for novel genes will be determined by the genetic findings and will make use of parallel studies in experimental animals.