title: Familial early-onset diabetes is not a typical MODY in several Tunisian patients.
abstract: BACKGROUND
  MODY (Maturity-onset diabetes of the young), a dominantly inherited form of early-onset diabetes, is clinically and genetically heterogeneous with more than ten genetic subtypes described worldwide.
  
  
  OBJECTIVE
  To evaluate the possible existence of MODY in 12 young diabetic Tunisian patients by searching for mutations in the most prevalent MODY genes.
  
  
  METHODS
  Twelve patients with diabetes in 2-to-3 generations, all diagnosed before age 31, were screened for mutations and deletions in HNF1A, HNF4A, INS, IPF1, NEUROD1 and GCK genes by Sanger sequencing and by Multiplex ligation-dependent probe amplification assay.
  
  
  RESULTS
  The patients had no evidence of autoimmunity and a mean age at diabetes diagnosis of 25.66 ± 3.96 years with severe overt diabetes (fasting glycaemia: 10.91 ± 3.55 mmol/ l; HbA1c: 10.46 ± 3.31 %). Two subjects were initially treated with insulin. On the ten initially treated with OHA or on diet, eight converted to insulin therapy (within 3 months to 20 years). Molecular analysis showed only one missense HNF4A mutation (I453V) in one family. No mutations in the studied genes were detected in the other patients.
  
  
  CONCLUSIONS
  A molecular defect in known MODY genes has been excluded in 11 patients with early-onset diabetes suggesting that other genetic causes may explain diabetes in these families. In such cases, new generation sequencing approaches may be well appropriate to identify specific molecular etiologies from extended families and to establish a strategy of molecular diagnostic of MODY in Tunisia.
authors.affiliation: Unit of Molecular Endocrinology, Sousse Faculty of Medicine, Tunisia.
authors.forename: Abdelbasset
authors.initials: A
authors.lastname: Amara
authors.forename: Molka
authors.initials: M
authors.lastname: Chadli-Chaieb
authors.forename: Hela
authors.initials: H
authors.lastname: Ghezaiel
authors.forename: Julien
authors.initials: J
authors.lastname: Philippe
authors.forename: Rim
authors.initials: R
authors.lastname: Brahem
authors.forename: Aurelie
authors.initials: A
authors.lastname: Dechaume
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.forename: Larbi
authors.initials: L
authors.lastname: Chaieb
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguele
authors.forename: Moez
authors.initials: M
authors.lastname: Gribaa
authors.forename: Martine
authors.initials: M
authors.lastname: Vaxillaire
mesh_terms: D000293:Adolescent; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D055815:Young Adult
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4