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

• DOI: 10.2337/db07-0859
• Publication Date: 2007-11-15T01:54:07Z
• Authors: Christine Bellann...; Claire Carette; Jean-Pierre Riveline; René Valéro; Jean-François Ga...; Etienne Larger; Yves Reznik; Pierre-Henri Ducl...; Agnès Sola; Agnès Hartemann-...; Pierre Lecomte; Lucy Chaillous; Marie Laloi-Michelin; Jean-Marie Wilhem; Pierre Cuny; Françoise Duron; Bruno Guerci; Nathalie Jeandidier; Helen Mosnier-Pudar; Michel Assayag; Danièle Dubois-L...; Gilberto Velho; José Timsit
• Keywords: HNF1A

The clinical expression of maturity-onset diabetes the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics hepatocyte nuclear factor 1-alpha (HNF1A) gene mutation.We analyzed mutations identified in 356 unrelated MODY3 patients, 118 novel mutations, and searched for correlations between genotype age at diagnosis diabetes.Missense prevailed dimerization DNA-binding domains (74%), while truncating were predominant transactivation domain (62%). majority (83%) located exons 1- 6, thus affecting three HNF1A isoforms. Age was lower patients with than those missense (18 vs. 22 years, P = 0.005). Missense dimerization/DNA-binding associated a (20 30 10(-4)). Patients isoforms younger involving one or two (P 0.03).These data show that part variability explained by type location mutations. These findings should considered studies search additional modifier factors.