MODY2 in Asia: analysis of GCK mutations and clinical characteristics

Aims: Heterozygous inactivating mutations in the GCK gene cause the familial, mild fasting hyperglycaemia named MODY2. Many patients with MODY2 in Asia have delayed timely treatment because they did not receive the correct diagn osis. This study aims to analyze the clinical characteristics and GCK mutations in Asian MODY2. Methods: We have collected 110 Asian patients with MODY2 from the PubMe d, Embase, Medline, Web of Science, CNKI, and Wanfang with the following s earch terms: ‘maturity-onset diabetes of the young’ OR ‘MODY’ OR ‘maturity-onset diabe tes of the young type 2’ OR ‘MODY2’ OR ‘GCK-DM’ OR ‘GCK-MODY’. Both mutations of GCK and clinical characteristics of MODY2 were analyzed. Results: There were 96 different mutations that occurred in coding regio ns and non-coding regions. Exon 5 and 7 were the most common location in coding regions and missense was the primary mutation type. The proportion of proba nds younger than 25 was 81.8%, and 81.4% of the probands had family history of hyperglycaemia. Ninety percent and 93% of Asian MODY2 probands exhibited mild elevatio n in FPG (5.4–8.3 mmol/L) and HbA1c (5.6–7.6%), respectively. Conclusions: In most Asian patients, MODY2 occurred due to GCK mutation in coding regions, and exon 5 and 7 were the most common locations. FPG, HbA1c, and familial diabetes were important reference indicators for diagnosing MOD Y2. Altogether, the study indicates that for the young onset of diabetes with mild elevat ed blood glucose and HbA1c and family history of hyperglycaemia, molecular genetic testing is suggested in order to differentiate MODY2 from other types of diabetes earlier.