title: Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus.
abstract: OBJECTIVE
  Six known genes responsible for maturity-onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early-onset type 2 diabetes.
  
  
  METHODS
  Fifty-one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha, GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non-diabetic controls, were classified as potentially pathogenic mutations.
  
  
  RESULTS
  We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the studied probands.
  
  
  CONCLUSIONS
  Mutations of the six known MODY genes may not be a major cause of MODY and early-onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early-onset type 2 diabetes.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. sinpv.natpl@gmail.com
authors.forename: Nattachet
authors.initials: N
authors.lastname: Plengvidhya
authors.forename: Watip
authors.initials: W
authors.lastname: Boonyasrisawat
authors.forename: Nalinee
authors.initials: N
authors.lastname: Chongjaroen
authors.forename: Prapaporn
authors.initials: P
authors.lastname: Jungtrakoon
authors.forename: Sutin
authors.initials: S
authors.lastname: Sriussadaporn
authors.forename: Sathit
authors.initials: S
authors.lastname: Vannaseang
authors.forename: Napatawn
authors.initials: N
authors.lastname: Banchuin
authors.forename: Pa-thai
authors.initials: PT
authors.lastname: Yenchitsomanus
mesh_terms: D000328:Adult; D017668:Age of Onset; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D000081410:Germinal Center Kinases; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D013785:Thailand / Q000453:epidemiology; D015534:Trans-Activators / Q000235:genetics; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000081410:Germinal Center Kinases; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D018398:Homeodomain Proteins; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; C496592:HNF4A protein, human; C093970:NEUROD1 protein, human; C084010:pancreatic and duodenal homeobox 1 protein