title: Mutations in the coding regions of the hepatocyte nuclear factor 4 alpha in Iranian families with maturity onset diabetes of the young.
abstract: Hepatocyte nuclear factor 4alpha (HNF4alpha) is a nuclear receptor involved in glucose homeostasis and is required for normal beta cell function. Mutations in the HNF4alpha gene are associated with maturity onset diabetes of the young type 1 (MODY1). The aim of the present study was to determine the prevalence and nature of mutations in HNF4alpha gene in Iranian patients with a clinical diagnosis of MODY and their family members. Twelve families including 30 patients with clinically MODY diagnosis and 21 members of their family were examined using PCR-RFLP method and in case of mutation confirmed by sequencing techniques. Fifty age and sex matched subjects with normal fasting blood sugar (FBS) and Glucose tolerance test (GTT) were constituted the control group and investigated in the similar pattern. Single mutation of V255M in the HNF4alpha gene was detected. This known mutation was found in 8 of 30 patients and 3 of 21 individuals in relatives. Fifty healthy control subjects did not show any mutation. Here, it is indicated that the prevalence of HNF4alpha mutation among Iranian patients with clinical MODY is considerable. This mutation was present in 26.6% of our patients, but nothing was found in control group. In the family members, 3 subjects with the age of <or=25 years old carried this mutation. Therefore, holding this mutation in this range of age could be a predisposing factor for developing diabetes in future.
authors.affiliation: 1Internal Medicine Department, Ghaem Hospital & Endocrine Research Center, Mashhad University of Medical Sciences, Parastar St, Ahmad abad blvd, Mashhad, Iran. taghavimr@mums.ac.ir
authors.forename: Seyed Morteza
authors.initials: SM
authors.lastname: Taghavi
authors.forename: Seyedeh Seddigheh
authors.initials: SS
authors.lastname: Fatemi
authors.forename: Houshang
authors.initials: H
authors.lastname: Rafatpanah
authors.forename: Rashin
authors.initials: R
authors.lastname: Ganjali
authors.forename: Jalil
authors.initials: J
authors.lastname: Tavakolafshari
authors.forename: Narges
authors.initials: N
authors.lastname: Valizadeh
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000235:genetics; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D009154:Mutation; D016366:Open Reading Frames; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4