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.
Aim: 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.
Conclusion: 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.