Clinical and molecular genetic analysis of one MODY2 family caused by novel glucokinase gene mutation
- VernacularTitle:葡萄糖激酶新发基因突变致MODY2一家系的临床及分子遗传学分析
- Author:
Tingjuan ZHENG
1
;
Tong ZHANG
1
;
Yuhuan WANG
1
Author Information
- Publication Type:Journal Article
- Keywords: maturity-onset diabetes of the young (MODY); glucokinase (GCK); gene mutation
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):1032-1036
- CountryChina
- Language:Chinese
- Abstract: [Objective] To report a Chinese family with maturity-onset diabetes of the young, type 2 (MODY2) caused by a novel glucokinase (GCK) gene mutation and to analyze its genetic and clinical characteristics. [Methods] Gene sequencing, clinical data collection and analysis were performed on a MODY2 family. [Results] A total of 18 members of this family were investigated, of whom 11 were diabetic, including the proband and her younger brother, father, uncle, cousin and other paternal members. The proband and her brother, father and uncle all had heterosense mutations of GCK gene (exon1: c.45G>A: p.K15K). Bioinformatics function prediction suggested that the mutation might affect mRNA splicing and lead to impaired GCK function. The mutation has not been reported in research on domestic population. The glycosylated hemoglobin levels of the proband and her younger brother were 6.49% and 6.72%; their fasting blood glucose levels were 6.80 mmol/L and 7.01 mmol/L, respectively. The diabetes autoantibody profiles were negative. Blood glucose levels remained stable during 6-18 months of follow-up. [Conclusion] The heterosense mutation of GCK gene in the MODY-2 family (exon1: c.45G>A: p.K15K) is a newly discovered mutation site in the Chinese population, and its clinical manifestations are mild, persistent and stable fasting hyperglycemia, and elevated glycosylated hemoglobin. The pathogenicity of GCK gene synonymous mutations should not be underestimated.
