The most common forms of diabetes, type 1 and type 2, result from an interaction of environmental triggers with the additive effects of several gene mutations that predispose the patient to diabetes. Rarer forms, collectively called monogenic diabetes, result from a mutation in a single gene that reduces the body's ability to manufacture insulin. In most cases, the patient inherits the genetic mutation from a parent, but sometimes mutations occur spontaneously. Scientists have identified several different genes that cause monogenic diabetes.
Neonatal Diabetes--Permanent
Neonatal diabetes occurs within the first six months of a baby's life. About half of all cases of neonatal diabetes are permanent, according to the National Institute of Diabetes and Digestive and Kidney Diseases. NIDDK lists seven genes that cause permanent neonatal diabetes: KCNJ11, ABCC8, GCK, IPF1, PTF1A, FOXP3 and EIF2AK3. KCNJ11 and ABCC8 can also cause transient neonatal diabetes. Mutations in KCNJ11 are the most common cause of permanent neonatal diabetes. Except for ABCC8, mutations in all of these other genes also cause intrauterine growth restriction. Babies need only one faulty copy of KCNJ11 or ABCC8 to develop permanent neonatal diabetes, while babies must carry two faulty copies of GCK, IPF1, PTF1A or EIF2AK3 to develop permanent neonatal diabetes. Because boys have only one X chromosome while girls have two, boys are more likely than girls to have permanent neonatal diabetes due to a mutation in FOXP3, which lies on the X chromosome. According to Online Mendelian Inheritance in Man, mutations in FOXP3 can also contribute to type 1 diabetes.
Neonatal Diabetes--Transient
Babies with transient neonatal diabetes have high blood sugar that resolves during infancy but can return again later in life. NIDDK lists four genes that can cause transient neonatal diabetes: ZAC/HYMA1, ABCC8, KCNJ11 and HNF1B. All are dominant mutations, meaning that a baby who has one faulty copy of the gene develops the condition. Mutations in ZAC/HYMA1 most often cause transient neonatal diabetes. Mutations in KCNJ11 rarely cause transient neonatal diabetes; they much more commonly cause the permanent type.
Maturity Onset of Diabetes in the Young
Maturity onset of diabetes in the young, commonly called MODY, usually begins in adolescents or young adults, although the condition might not be diagnosed for several years. According to the NIDDK, about 1 to 5 percent of all cases of diabetes in the United States result from MODY. MODY is highly heritable, meaning that family members of people with MODY have a high risk of developing it themselves. A parent with MODY has a 50 percent chance of passing the condition to their children, says the NIDDK. NIDDK lists six genes that cause MODY: HNF4A, GCK, TCF1, TCF2, IPF1, and NeuroD1 (also called BETA2). All are dominant mutations. GCK and IPF1 can also cause permanent neonatal diabetes. According to Online Mendelian Inheritance in Man, mutations in TCF1 can also contribute to Type 1 diabetes. Most cases of MODY result from TCF1 mutation, with GCK mutation being the second most common cause. All other gene mutations are very rare causes of MODY, collectively accounting for about 33 percent of all cases.
