Abstract
BackgroundThere is scarcity of information on the clinical features and genetics of glucokinase-maturity-onset diabetes of the young (GCK-MODY) in China. The aim of the study was to investigate the clinical and molecular characteristics of Chinese children with GCK-MODY.MethodsEleven children with asymptomatic hyperglycemia and clinically suspected GCK-MODY were identified from the database of children with diabetes in the biggest children’s hospital in South China. Clinical data were obtained from medical records. Blood was collected from the patients and their parents for glucokinase (GCK) gene analysis. Parents without diabetes were tested for fasting glucose and HbA1c. Clinical information and blood for GCK gene analysis were obtained from grandparents with diabetes. GCK gene mutational analysis was performed by polymerase chain reaction and direct sequencing. Patients without a GCK gene mutation were screened by targeted next-generation sequencing (NGS) technology for other MODY genes.ResultsNine children tested positive for GCK gene mutations while two were negative. The nine GCK-MODY patients were from unrelated families, aged 1 month to 9 years and 1 month at first detection of hyperglycaemia. Fasting glucose was elevated (6.1–8.5 mmol/L), HbA1c 5.2–6.7% (33.3–49.7 mmol/mol), both remained stable on follow-up over 9 months to 5 years. Five detected mutations had been previously reported: p.Val182Met, c.679 + 1G > A, p.Gly295Ser, p.Arg191Gln and p.Met41Thr. Four mutations were novel: c.483 + 2 T > A, p.Ser151del, p.Met57GlyfsX29 and p.Val374_Ala377del. No mutations were identified in the other two patients, who were also tested by NGS.ConclusionsGCK gene mutations are detected in Chinese children and their family members with typical clinical features of GCK-MODY. Four novel mutations are detected.
Highlights
There is scarcity of information on the clinical features and genetics of glucokinase-maturity-onset diabetes of the young (GCK-Maturity-onset diabetes of the young (MODY)) in China
One of the most common types reported is MODY2, which is caused by heterogenous inactivating mutations in the glucokinase (GCK) gene, known as glucokinase-maturity-onset diabetes of the young (GCK-MODY) [1]
The fasting glucose falls in the range 5.6–8.0 mmol/L with hemoglobin A1c (HbA1c) 5.6–7.3% (38–56 mmol/mol) in those aged 40 years and below, as shown in a large cohort of GCKMODY patients [3]
Summary
There is scarcity of information on the clinical features and genetics of glucokinase-maturity-onset diabetes of the young (GCK-MODY) in China. Maturity-onset diabetes of the young (MODY) is a rare form of diabetes mellitus with autosomal dominant inheritance, typically diagnosed before 25 years of age. It is caused by mutations in 13 genes involved in pancreatic β-cell function [1]. Glucokinase (GCK) is a key enzyme in the regulation of insulin release in pancreatic β-cells. It is encoded by the glucokinase gene located at chromosome 7p15.3– p15.1, consisting of 10 exons and spanning 45,168 bp [4]. Heterozygous activating mutations cause persistent hyperinsulinemic hypoglycaemia of infancy [4]
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