A novel unstable mutation in mitochondrial DNA responsible for maternally inherited diabetes and deafness.

Sylvie Bannwarth, Meriame Abbassi, René Valéro, Konstantina Fragaki, Noémie Dubois, Bernard Vialettes, Véronique Paquis-Flucklinger

Department of Medical Genetics, Archet 2 Hospital, Centre Hospitalier Universitaire de Nice, Nice, France.

Diabetes care 2011 Dec

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The m.3243A>G mutation in mitochondrial DNA (mtDNA) is responsible for maternally inherited diabetes and deafness (MIDD). Other mtDNA mutations are extremely rare. We studied a patient presenting with diabetes and deafness who does not carry the m.3243A>G mutation. We identified a deficiency of respiratory chain complex I in the patient's fibroblasts. mtDNA sequencing revealed a novel mutation that corresponds to an insertion of one or two cytosine residues in the coding region of the MT-ND6 gene (m.14535_14536insC or CC), leading to premature stop codons. This heteroplasmic mutation is unstable in the patient's somatic tissues. We describe for the first time an unstable mutation in a mitochondrial gene coding for a complex I subunit, which is responsible for the MIDD phenotype. This mutation is likely favored by the m.14530T>C polymorphism, which is homoplasmic and leads to the formation of an 8-bp polyC tract responsible for genetic instability.

Citation

Sylvie Bannwarth, Meriame Abbassi, René Valéro, Konstantina Fragaki, Noémie Dubois, Bernard Vialettes, Véronique Paquis-Flucklinger. A novel unstable mutation in mitochondrial DNA responsible for maternally inherited diabetes and deafness. Diabetes care. 2011 Dec;34(12):2591-3