Abstract:

Objective Objective To determine phenotype and genetic characteristics of monogenic diabetes in children. Methods Clinical manifestations and laboratory data at initial diagnosis of 76 children with diabetes admitted to our department from August 2020 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed in 21 patients with suspected monogenic diabetes. Results A total of seven cases of monogenic diabetes were identified by whole exome sequencing (WES), all of which were maturity-onset diabetes of the young (MODY). Three cases of MODY2 were caused by GCK variants, and three cases of MODY3 were caused by HNF1A variants and one case of MODY10 caused by INS variant. Two novel variants were identified, including c.1124T>G (p.V375G) in GCK and c.110A>T (p.E37V) in INS. Five of the 7 patients (5/7) with MODY had no typical symptoms of diabetes and were admitted to the hospital due to incidentally elevated glucose level. The level of blood glucose and glycosylated hemoglobin in the MODY group (n=7) were lower than those in the T1DM group (n=62) (P<0.05), and showed no significant difference compared with those of T2DM group (n=7). The levels of insulin and C-peptide in the MODY group were higher than those in the T1DM group (P<0.05), and were significantly lower than those in the T2DM group (P<0.05). In addition, a T1DM child with retarded mental development received an additional diagnosis of 18p deletion syndrome by WES, and another T2DM child with sustained elevated liver aminotransferase received an additional diagnosis of Wilson Disease by WES. Conclusions MODY is the common type of monogenic diabetes. This study expands the mutation spectrum of MODY. When diabetes patient present with extra-pancreatic manifestations, the combination of other genetic disorders should be considered.

Key words: whole exome sequencing, monogenic diabetes, maturity-onset diabetes of the young