Objective: To know more about the etiology and mechanism of antibody-negative diabetes, screening MODY pathogenicity genes and deepening understanding of islet autoantibody-negative diabetes, so as to individualized precision treatment.
Methods: A total of 31 subjects with diabetes who had negative islet autoantibodies and C-peptide ≥0.3 ng/ml were collected. Another group was the type 1 diabetes control group, After informed consent obtained patient history data and a detailed physical examination. Peripheral blood DNA was extracted from patients with antibody negative, and peripheral blood DNA was extracted from parents as necessary for high-throughput sequencing of glucose metabolism related genes. Sanger sequencing validation was performed on patients and their families for the possible pathogenic mutations that were screened. The relative indexes such as birth weight, fasting C-peptide, onset time, initial HbA1c, age, family history, The incidence of DKA, insulin dosage and statistical analysis.
Results: 1) In the 31 cases, 20 cases of diabetic patients detected possible related mutations, 11 patients were not detected mutation genes. There were 11 genes related to single gene diabetes mellitus, of which 3 were pathogenic variation, 1 were possible pathogenic variation, 3 were likely to be benign and 4 the pathogenicity is not clear. There were 12 genes related to susceptibility to diabetes. 2) There was a significant difference in the BMI, fasting C-peptide, DKA incidence and insulin dosage between the group with pathogenic mutation and the group with positive islet autoantibody (P<0.05).There was a significant difference in BMI, fasting C-peptide, HbA1c and insulin dosage between the group of undetected gene mutation and the group of positive islet autoantibodies (P<0.05). There was a significant difference in the BMI, fasting C-peptide, DKA incidence and insulin dosage between the group with pathogenic mutation group and undetected gene mutation group (P<0.01).
Conclusions: 1) there is a single gene mutation in Islet autoantibodies negative diabetes children group. However, single-gene diabetic genetic variation may not be the main cause of antibody-negative diabetes. 2) This study found that GCGR c.118G>A p.G40S exists in Chinese patients with T2DM, considering that the locus is related to the susceptibility to T2DM in China. 3) Our study found a case of non-reported ELN nonsense mutation (G611 *), this mutation may be related to glucose metabolism. 4) This study found an unreported frameshift mutation of LIPC, which had a great effect on the protein and was related to glucose and lipid metabolism.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology