What is the difference between the SUR1 gene mutation and the KIR6 gene mutation?

Great question. Mutations in DNA – the genes – are like software errors. ABCC8 (SUR1 protein) and KCNJ11 (Kir6.2 protein) are both genes that “code for” the two proteins that together make up the KATP channel. Since they are different proteins, they differ in what tissues in the body they are found, and to what extent, besides the insulin secreting cells. The word “mutation” in the question should be plural. Think of both genes as a string of pearls, with four colors. Any pearl could be a wrong color, a mutation, but some of them have no effect at all – they are neutral – some of them are mild, and some are devastating when it comes to “translating” the gene sequence of pearls into the string that forms the proteins – made up of 26 amino acids. This is called the genetic code. The more we learn about the mutations, the more different patterns we see. Mutations in SUR1 (ABCC8 gene) are more often associated with low blood sugars at birth – persistent hypoglycemia, often needing surgery in the infant. KCNJ11 (Kir6.2 protein) mutations are more often associated with neonatal diabetes, but now we know that mutations in either one can cause permanent neonatal diabetes, transient neonatal diabetes and, rarely, MODY-type diabetes. KCNJ11 mutations are also more clearly associated in some specific mutations with learning disorders, developmental delay, and seizures. In our own studies of neonatal diabetes, we have found far more cases due to KNCJ11/Kir6.2 mutations than ABCC8/SUR1 mutations. A great deal of more specific information can be found at Dr. Hattersley’s web site on GENETIC TYPES OF DIABETES INCLUDING MATURITY-ONSET DIABETES OF THE YOUNG (MODY). The newest gene that can cause neonatal diabetes is insulin itself; we published that just last fall (see Insulin Mutation Screening in 1044 Patients with Diabetes: Mutations in the INS gene are a Common Cause of Neonatal Diabetes but a Rare Cause of Diabetes Diagnosed in Childhood or Adulthood.) It also has to be considered in any patient negative for KNCJ11 and ABCC8 mutations, but it is actually more common than the ABCC8 mutations in this disease.

LP