Background: Monogenic diabetes is a heterogeneous group of metabolic disorders resulting from defects in single genes. Over 90% of the subjects remain undiagnosed, mainly because of lack of access to genetic testing.
Objective and hypotheses: The aim of our study was to do a comprehensive genetic analysis of the whole pediatric and young adult autoimmune antibody negative diabetes population of Lithuania.
Method: 860 children (age 018 years) and 349 young adults (age >1825 years) with diabetes were screened for the presence of islet autoimmune antibodies. Genetic analyses were performed in 147 subjects, 80 of them had no detectable autoimmune antibodies and 67 had positive IAA antibodies only. We included the IAA positive probands under insulin treatment, because the antibodies were tested after introduction of insulin. Genetic analysis was performed by high throughput sequencing of DNA of 323 genes involved in diabetes and pancreas development.
Results: We have analyzed 147 diabetic subjects with suspected monogenic diabetes. Four had neonatal diabetes (onset < 6 months of age), 134 pediatric onset (>6 months to 18 years) and 10 had diabetes onset between 1825 years. Genetic analysis revealed mutations/variants in known MODY genes in 25.9% of the probands: 13.6% had mutations in the GCK, 4.8% in the HNF1A, 2% in the HNF4A, 1.4% in the ABCC8, 1% in the INS and 1% in the KLF11 genes, overall we detected 12 novel variants. In addition, in 36.7% of the probands, we found variants in potential diabetes genes with a high-predicted pathogenicity.
Conclusion: This testing approach yields a high rate of positive results. In the whole Lithuanian pediatric diabetic and young adult population (1209 probands), GCK mutations are found in 1.65%, HNF1A mutations in 0.6% and HNF4A mutations in 0.25% of the patients.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology