title: High frequency of mutations in MODY and mitochondrial genes in Scandinavian patients with familial early-onset diabetes.
abstract: OBJECTIVE
  To investigate the contribution of mutations in maturity-onset diabetes of the young (MODY) and mitochondrial genes to early-onset diabetes with a strong family history of diabetes in a cohort with a high prevalence of Type I (insulin-dependent) diabetes mellitus.
  
  
  METHODS
  Screening for sequence variants in the hepatocyte nuclear factor (HNF)-4alpha (MODY1), glucokinase (MODY2), HNF-1alpha (MODY3) genes and mitochondrial DNA was carried out in 115 Finnish and Swedish patients with early-onset ( </= 40 years) diabetes using the single strand conformation polymorphism (SSCP) technique and direct sequencing. Allele frequencies were compared with 118 patients with onset of diabetes Type II (non-insulin-dependent) diabetes mellitus after the age of 40 and 92 non-diabetic control subjects without a family history of diabetes.
  
  
  RESULTS
  In total 52 sequence variants were found in the HNF-1alpha, HNF-4alpha and glucokinase genes, 12 of which were considered as MODY mutations. Three families had the A3243G mutation in the mitochondrial tRNA(Leu) gene, which resulted in an overall prevalence of these mutations of 13 %.
  
  
  CONCLUSIONS
  Among 115 Scandinavian families, mutations in the HNF-1alpha gene represented the most common cause of familial early-onset ( </= 40 years) diabetes: MODY3 (5.2 %) more than MODY2 (3.5 %) more than MIDD (2.6 %) more than MODY1 (1.7 %).
authors.affiliation: Department of Endocrinology, University Hospital MAS, University of Lund, Malmö, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lehto
authors.forename: C
authors.initials: C
authors.lastname: Wipemo
authors.forename: S A
authors.initials: SA
authors.lastname: Ivarsson
authors.forename: C
authors.initials: C
authors.lastname: Lindgren
authors.forename: M
authors.initials: M
authors.lastname: Lipsanen-Nyman
authors.forename: J
authors.initials: J
authors.lastname: Weng
authors.forename: L
authors.initials: L
authors.lastname: Wibell
authors.forename: E
authors.initials: E
authors.lastname: Widén
authors.forename: T
authors.initials: T
authors.lastname: Tuomi
authors.forename: L
authors.initials: L
authors.lastname: Groop
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004272:DNA, Mitochondrial / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005091:Exons; D005190:Family; D005260:Female; D014644:Genetic Variation; D005941:Glucokinase / Q000235:genetics*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D012537:Scandinavian and Nordic Countries; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D005941:Glucokinase