Résumé

PA-065

A novel mutation MT-COIII m.9267G>C and MT-COI m.5913G>A mutation in mitochondrial genes in a Tunisian family with maternally inherited diabetes and deafness (MIDD) associated with sever nephropathy

M. Tabebi*^a (Mlle), E. Mkaouar-Rebai^a (Dr), M. Mnif^b (Dr), F. Kallabi^a (M.), A. Ben Mahmoud^a (M.), W. Ben Saad^b (Dr), N. Charfi^b (Dr), L. Keskes-Ammar^a (Pr), H. Kamoun^a (Pr), M. Abid^b (Pr), F. Fakhfakh^a (Pr)

^a Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax. Tunisia, Sfax, TUNISIE ; ^b Service d’endocrinologie, C.H.U. Habib Bourguiba de Sfax, Tunisia, Sfax, TUNISIE

* mounamouna62@yahoo.fr

Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia, maternal transmission and its association with a bilateral hearing impairment. Several studies reported mutations in mitochondrial genes as potentially pathogenic for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells.

In the present report, we studied a Tunisian family with mitochondrial diabetes (MD) and deafness associated with nephropathy. The mutational analysis screening revealed the presence of a novel heteroplasmic mutation m.9276G>C in the mitochondrial COIII gene, detected in mtDNA extracted from leukocytes of a mother and her two daughters indicating that this mutation is maternally transmitted and suggest its implication in the observed phenotype.

Bioinformatic tools showed that m.9267G>C mutation (p.A21P) is « deleterious » and it can modify the function and the stability of the MT-COIII protein by affecting the assembly of mitochondrial COX subunits and the translocation of protons then reducing the activity of the respective OXPHOS complexes of ATP synthesis.The nonsynonymous mutation (p.A21P) has not been reported before, it is the first mutation described in the COXIII gene which is related to insulin dependent mitochondrial diabetes and deafness and could be specific to the Tunisian population. The m.9267G>C mutation was present with a nonsynonymous inherited mitochondrial homoplasmic variation MT-COI m.5913 G>A (D4N) responsible of high blood pressure, a clinical feature detected in all explored patients.

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