Résumé :
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Mitochondrial diseases are a wide group of disorders characterized by genetic or biochemical abnormalities of the oxidative phosphorylation. They may depend on mitochondrial DNA as well as on nuclear genome defects. Mitochondrial DNA related disorders encompass an increasing number of clinical pictures associated with more than 250 different provisional or confirmed pathogenic changes in mtDNA. The clinical features are usually extremely heterogeneous because the mitochondrial diseases may involve several tissues with different degrees of severity and patients may present with a wide range of clinical features in various combinations. The complexity of this clinical and genetic heterogeneity of the mitochondrial disorders makes the genotype-phenotype correlation difficult. Muscle and brain are mostly affected, probably because of their high dependence on oxidative metabolism. Thus, neurological impairment is a hallmark feature of such disorders. In the present study, we described a patient with severe form of mitochondrial myopathy. In fact, he presented a psychomotor and neurodevelopmental regression, generalized clonic seizure, progressive tetraplegia, leucodystrophy and congenital deafness. Brain MRI showed mild hyperintensity of posterior periventicular white matter, involvement of the interpeduncular nucleus and central tegmental tract, white matter abnormalities and cerebellar atrophy. He also suffered from a central blindness and swallowing difficulty. The whole mitochondrial genome screening in this patient revealed the presence of 19 reported polymorphisms and a heteroplasmic novel G to A mutation at nucleotide 8411 of the mitochondrial DNA. This novel mutation substitutes a Methionine to Valine (p.M16V) in a highly conserved region of the mitochondrial ATPase 8 protein which is one of the chains of the mitochondrial ATP synthase complex which is responsible for most of the ATP production in cells. Not surprisingly, mutations that affect the functioning of the ATP synthase in humans are responsible for a mitochondrial dysfunction and may be pathogenic. This novel mutation was detected in heteroplasmic form (97 %) and was absent in the mother and the two sister of the proband but also in 120 Tunisian controls. Thus, the de novo p.M16V mutation could strongly be associated to the disease in the tested patient.
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