Résumé :
|
Mitochondrial cytopathies are a group of multi-systemic diseases exhibiting biochemical, histological and/or genetic evidence of mitochondrial dysfunction. These diseases include syndromes caused by molecular defects in mitochondrial DNA (mtDNA) which may vary from punctual mutations to larger rearrangements such as duplications or deletions. Kearns Sayre syndrome (KSS) is a mitochondrial disorder characterized by the emergence before the age of 20 years of progressive external ophthalmoplegia, pigmentary retinopathy, with other heterogeneous clinical manifestations, including cardiac conduction defects, muscle abnormalities, sensorineural hearing loss and endocrinopathies. The mtDNA deletions associated to this syndrome are variable in size and location. They range from 1.3 to 8 kb with different amounts of deleted mtDNA in different tissues which correlates with the multi-systemic nature of the syndrome. The present study reported a patient with typical features of KSS. The long-range PCR amplification of the mitochondrial DNA extracted from blood leukocytes, buccal mucosa and hair follicles of the studied patient showed the presence of two uncommon heteroplasmic mtDNA 9.768 kb and 7.253 kb deletions spanning respectively nucleotides 6124 to 15893 and 8572 to 15826. We also detected the common heteroplasmic deletion of 4977 bp spanning nucleotides 8469 and 13447 in the 3 tested tissues. In addition, the sequencing of the whole mitochondrial genome showed the presence of 18 known polymorphisms and the m.9438G>A mutation in the COXIII gene which classified the studied patient under the haplogroup N*.
|