Résumé :
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Genetic alterations of the catalytic subunit of the polymerase gamma gene (POLG) have been recently involved in very diverse clinical diseases ranging from early severe Alpers-Huttenlocher syndrome to late adult diseases presenting with a very diverse combination of ophthalmoplegia, ataxia, epilepsy, peripheral neuropathy, gastro-intestinal symptoms, psychiatric disturbances, Parkinson syndrome... Polymerase gamma is the sole DNA polymerase that is responsible for the replication of mitochondrial DNA. Its reported mutations have been very diverse, affecting any of the three functional domains of the protein (polymerase catalytic, exonuclease or linker domains). They have been associated with recessive as well as dominant inheritance. Furthermore several POLG mutations have significant frequency in the general population despite in vitro demonstration of their impact on the protein function and/or stability. In conclusion mutations of the POLG gene appear to be a major cause of a number of human neuromuscular disorders, the range of which remains to be determined. We here report the clinical, electrophysiological, and muscle histological characteristics of a series of 10 patients with severe sensory ganglionopathy as prominent clinical presentation. These investigations allowed to diagnose the mitochondrial origin of the disease. Genetic analyses demonstrated the presence of POLG mutations with recessive inheritance in most of these patients. Severe sensory ganglionopathy should thus be considered as a clinical presentation highly suggestive of POLG mutations.
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