Résumé :
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Communication n° 684 Introduction : Multiple deletions of mitochondrial DNA (mtDNA) were first reported in families with autosomal dominant inherited progressive external ophtalmoplegia (ad-PEO). Since that time, multiple mtDNA deletions were also found in recessive forms of PEO and in many sporadic cases with variable clinical features, constantly including PEO. Recently, mutations in three nuclear genes were identified in ad-PEO : in the gene encoding the adenine nucleotide translocator (ANT1), in the helicase protein Twinkle gene and in DNA polymerase gamma (POLG)gene. Those families were linked to chromosomes 4q34-35, 10q23.3-q24.3 and 15q22-q26 respectively. Aims : To report on the cases of 12 patients in three families without any progressive external ophtalmoplegia. Methods : We personnally evaluated and followed 12 patients in 3 families with clinical and histological features of autosomal dominant mitochondriopathy. Southern BLot study on muscle biopsy fragments and white blood cells mtDNA was performed. A genetic screening of the usually 3 implicated genes was performed. Results : A wide phenotype varibility was noticed, with striking features of spino-cerebellar ataxia and frontal dementia in several individuals of the first family. In the second family, a more greater variability existed since one individual presented with clinical features of neuro-inflammatory pathology, whereas her child presented with optic atrophy and neuropathy. In the last family, the two affected siblings presented with limb girdle proximal myopathy . The histological study of muscular biopsies revealed classical features of mitochondripathy. In all cases, southern blot revealed multiple deletions.Screening of ANT1, Twinkle and POLG gene failed to show any mutations. Conclusion : This study gives grounds for suggesting that mitochondriopathy of mendelian inheritance can be evoked with spino-cerebellar ataxia, in the absence of PEO. and that at least a fourth locus should exist.
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