Insulin Mutation Screening in 1,044 Patients With Diabetes Mutations in the INS Gene Are a Common Cause of Neonatal Diabetes but a Rare Cause of Diabetes Diagnosed

OBJECTIVE—Insulin gene (INS) mutations have recently been described as a cause of permanent neonatal diabetes (PND). We aimed to determine the prevalence, genetics, and clinical pheno-type of INS mutations in large cohorts of patients with neonatal diabetes and permanent diabetes diagnosed in infancy, child-hood, or adulthood. RESEARCH DESIGN AND METHODS—The INS gene was sequenced in 285 patients with diabetes diagnosed before 2 years of age, 296 probands with maturity-onset diabetes of the young (MODY), and 463 patients with young-onset type 2 diabetes (nonobese, diagnosed 45 years). None had a molecular genetic diagnosis of monogenic diabetes. RESULTS—We identified heterozygous INS mutations in 33 of 141 probands diagnosed at 6 months, 2 of 86 between 6 and 12 months, and none of 58 between 12 and 24 months of age. Thre