The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Diabetes Année : 2008

The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3

(1) , (2) , (3, 4) , (5) , (6) , (7, 8) , (9, 10) , (11) , , , (12) , (13, 14) , (15) , , (16) , , (17) , (18, 19) , , , (20, 2, 21, 8, 22) , (23) , (21)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Christine Bellanné-Chantelot
Claire Carette
Agnès Sola-Gazagnes
  • Fonction : Auteur
Agnès Hartemann-Heurtier
  • Fonction : Auteur
Jean-Marie Wilhem
  • Fonction : Auteur
Françoise Duron
  • Fonction : Auteur
Helen Mosnier-Pudar
  • Fonction : Auteur
Michel Assayag
  • Fonction : Auteur

Résumé

OBJECTIVE—The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation.

RESEARCH DESIGN AND METHODS—We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes.

RESULTS—Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10−4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03).

CONCLUSIONS—These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors.

Fichier non déposé

Dates et versions

hal-03275383 , version 1 (01-07-2021)

Identifiants

Citer

Christine Bellanné-Chantelot, Claire Carette, Jean-Pierre Riveline, René Valéro, Jean-François Gautier, et al.. The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3. Diabetes, 2008, 57 (2), pp.503 - 508. ⟨10.2337/db07-0859⟩. ⟨hal-03275383⟩
24 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook Twitter LinkedIn More