A homozygous mutation in the insulin gene (INS) causing autosomal recessive neonatal diabetes in Saudi families.

purposeInsulin gene (INS) mutations are a rare cause of permanent neonatal diabetes and mature-onset diabetes of the young (MODY10). Homozygous mutations have been reported to cause diabetes by decreasing insulin biosynthesis through distinct mechanisms. In this study, we report a homozygous mutation c.-331C>G in the INS gene causing autosomal recessive neonatal diabetes in Saudi families and share our experience with diagnosis and management.

methodsWe retrospectively reviewed all cases diagnosed with diabetes during the first week of life. We identified 18 cases, and all underwent genetic testing to identify the cause. Most had mutations in common genes (9 in KCNJ11 and 5 in ABCC8). The inclusion criterion for this study was a mutation in the INS gene.

resultsFour patients from 3 Saudi families had mutations in the INS gene. All patients were born with low birth weight and were diagnosed with neonatal diabetes at the age of 2 days. Sanger sequencing analysis identified a homozygous INS pathogenic promoter variant, c.-331C>G. All patients were managed by insulin therapy. Two patients had persistent diabetes and in 2 cases diabetes resolved.

conclusionThis report indicates that a homozygous mutation in the INS gene is a probable and important cause of neonatal diabetes in Saudi Arabia. The c.-331C>G variant in the INS gene identified in our study showed variability both within and between families and different outcomes ranging from early resolution of diabetes after 2 months of life to permanent diabetes.