title: Glucokinase gene mutations (MODY 2) in Asian Indians.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 Madras Diabetes Research Foundation , Chennai, India .
authors.forename: Sekar
authors.initials: S
authors.lastname: Kanthimathi
authors.forename: Suresh
authors.initials: S
authors.lastname: Jahnavi
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Balamurugan
authors.forename: Harish
authors.initials: H
authors.lastname: Ranjani
authors.forename: Jagadesan
authors.initials: J
authors.lastname: Sonya
authors.forename: Soumik
authors.initials: S
authors.lastname: Goswami
authors.forename: Subhankar
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Radha
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000235:genetics*; D007194:India / Q000453:epidemiology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040242:Risk Reduction Behavior; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005941:Glucokinase