Detection and analysis of glucose metabolism-related genes in childhood diabetes using targeted next-generation sequencing: In pediatric population-a hospital-based study.

The aim of the present study was to explore the genetic causes of antibody-negative diabetes and investigate its characteristics. A total of 64 patients with new-onset diabetes (>6 m, <16 y) were identified and their initial clinical characteristics were analyzed. Of which, 32 cases with autoantibody-negative diabetes (male, 16 cases; female, 16 cases) were screened for auto-antibodies, including islet cell antibody, glutamic acid decarboxylase antibody and islet antigen-2, which were negative, and fasting C-peptide was ≥0.3 ng/ml. Peripheral blood DNA was extracted from the subjects and their parents for high-throughput sequencing of glucose metabolism-related genes. The group with the pathogenic variation was used as the experimental group. The control group comprised 32 cases of type 1 diabetes (T1D). Their baseline clinical characteristics were determined and statistically analyzed. Out of the 32 antibody-negative diabetes cases, 21 had possible related mutations. There were 2 HNF1B missense mutations, 1 GCK missense mutation and 1 de novo KCNJ11 missense mutation. GCGR c.118G>A p.G40S was present in patients with type 2 DM (T2DM); the locus is associated with T2DM susceptibility in China. An LIPC frameshift mutation was identified, which had not been previously reported; the gene was found to markedly affect protein function and be associated with glucose and lipid metabolism. It was concluded that children with antibody-negative T1D have monogenic diabetes. The present findings shed light on the etiology and mechanism of antibody-negative diabetes, which will enable the comprehensive analysis of antibody-negative diabetes genotypes and phenotypes and further help improved precision treatment.