Glucokinase Gene Mutations (MODY 2) in Asian Indians

Kanthimathi, S and Jahnavi, S and Balamurugan, K and Ranjani, H and Sonya, J and Goswami, S and Chowdhury, S and Mohan, V and Radha, V (2014) Glucokinase Gene Mutations (MODY 2) in Asian Indians. Diabetes Technology & Therapeutics, 16 (3). p. 180. ISSN 1520-9156



Abstract Background and Aim: Heterozygous inactivating mutations in the glucokinase (GCK) gene cause a hyperglycemic condition termed maturity-onset diabetes of the young (MODY) 2 or GCK-MODY. This is characterized by mild, stable, usually asymptomatic, fasting hyperglycemia that rarely requires pharmacological intervention. The aim of the present study was to screen for GCK gene mutations in Asian Indian subjects with mild hyperglycemia. Subjects and Methods: Of the 1,517 children and adolescents of the population-based ORANGE study in Chennai, India, 49 were found to have hyperglycemia. These children along with the six patients referred to our center with mild hyperglycemia were screened for MODY 2 mutations. The GCK gene was bidirectionally sequenced using BigDye(®) Terminator v3.1 (Applied Biosystems, Foster City, CA) chemistry. In silico predictions of the pathogenicity were carried out using the online tools SIFT, Polyphen-2, and I-Mutant 2.0 software programs. Results: Direct sequencing of the GCK gene in the patients referred to our Centre revealed one novel mutation, Thr206Ala (c.616A>G), in exon 6 and one previously described mutation, Met251Thr (c.752T>C), in exon 7. In silico analysis predicted the novel mutation to be pathogenic. The highly conserved nature and critical location of the residue Thr206 along with the clinical course suggests that the Thr206Ala is a MODY 2 mutation. However, we did not find any MODY 2 mutations in the 49 children selected from the population-based study. Hence prevalence of GCK mutations in Chennai is <1:1,517. Conclusions: This is the first study of MODY 2 mutations from India and confirms the importance of considering GCK gene mutation screening in patients with mild early-onset hyperglycemia who are negative for β-cell antibodies.

Item Type:Article
Official URL/DOI:
Uncontrolled Keywords:MODY 2, Gene mutation, Asian Indian
Subjects:Genetics and Diabetes > Maturity-Onset Diabetes of the Young(MODY)
Genetics and Diabetes
Diabetology > Diabetes Mellitus Type 2
Divisions:Department of Cell and Molecular Biology
Department of Advanced Research Biochemistry
Department of Islet Cell Transplantation
ID Code:792
Deposited By:surendar radha
Deposited On:19 Mar 2014 12:34
Last Modified:19 Mar 2014 12:34

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