title: Frequency of HNF4A-P.I463V Variant in the Tunisian North-African Population and Its Relation with Diabetes Mellitus.
abstract: BACKGROUND
  HNF4A-p.I463Vvariant, reported previously in two distinct families suspected of MODY-1, is assessed in this report to determine whether it is a mutation or a polymorphism (frequency >1%).
  
  
  METHODS
  200 Tunisian healthy people were screened for the presence of HNF4A-p.I463V variant, using RFLP-PCR technique and sequencing. Then, the frequency of this variant was estimated in the Tunisian population and compared to other populations registered in genetic databases. We also performed in-silico analysis using PolyPhen2 and Mutation T@sting softwares to assess the probable effect of HNF4A-p.I463V variant.
  
  
  RESULTS
  HNF4A-p.I463V had a rare frequency in different populations and was found in 3 control subjects (1.5%) of the studied population. PolyPhen2 predicted that it is a polymorphism, whereas mutation T@sting suggested a probably affected mutant protein.
  
  
  CONCLUSIONS
  HNF4A-p.I463V has a relatively high frequency (>1%) in our control cohort. It is also present in different ethnicities and in- silico analysis showed conflicting results. For these reasons, HNF4A-p.I463V should not be considered as a mutation responsible for MODY-1.
authors.affiliation: Unit of Molecular Endocrinology, Sousse Faculty of Medicine, University of Sousse, Sousse, Tunisia ; Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia ; Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.
authors.forename: Abdelbasset
authors.initials: A
authors.lastname: Amara
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia ; Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.
authors.forename: Ilhem
authors.initials: I
authors.lastname: Ben Charfeddine
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia ; Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.
authors.forename: Houda
authors.initials: H
authors.lastname: Ghédir
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia ; Higher Institute of Biotechnology of Monastir, University of Monastir, Tunisia.
authors.forename: Ons
authors.initials: O
authors.lastname: Mamaï
authors.affiliation: Regional Center of Blood Transfusion of Sousse, Sousse, Tunisia.
authors.forename: Saloua
authors.initials: S
authors.lastname: Jemni-Yacoub
authors.affiliation: Dept. of Endocrinology and Diabetology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Larbi
authors.initials: L
authors.lastname: Chaieb
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Ali
authors.initials: A
authors.lastname: Saad
authors.affiliation: Unit of Molecular Endocrinology, Sousse Faculty of Medicine, University of Sousse, Sousse, Tunisia ; Dept. of Endocrinology and Diabetology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Molka
authors.initials: M
authors.lastname: Chadli-Chaieb
authors.affiliation: Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia.
authors.forename: Moez
authors.initials: M
authors.lastname: Gribaa
keywords: HNF4A-p.I463V; MODY; Mutation; Polymorphism; Tunisia; Type 2 diabetes; in-silico; rs147638455