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Late‐onset mitochondrial DNA depletion: DNA copy number, multiple deletions, and compensation
Author(s) -
Barthélémy Cyrille,
Ogier De Baulny Hélène,
Diaz Jorge,
Armelle Cheval Marie,
Frachon Paule,
Romero Norma,
Goutieres Françoise,
Fardeau Michel,
Lombès Anne
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.1002
Subject(s) - mitochondrial dna , southern blot , mitochondrial myopathy , biology , polymerase chain reaction , myopathy , kearns–sayre syndrome , mitochondrial disease , microbiology and biotechnology , genetics , dna , gene
Through a report of 4 late‐onset cases with mitochondrial DNA (mtDNA) depletion, we address the specificity of the clinical entities associated with a very low residual amount of mtDNA. Three of the patients met the diagnostic criteria of Kearns Sayre syndrome, which has never been associated with mtDNA depletion. The fourth patient had an isolated skeletal myopathy. Deleted mtDNA molecules were found by long‐range polymerase chain reaction (PCR) only in the Kearns Sayre syndromes, which strengthens the clinical differences between the two types of patients. All patients had extremely low residual amounts of mtDNA as shown by Southern blot analysis. Using an original method based on competitive PCR, we were able to measure the number of mtDNA copies per diploid genome. These results demonstrated the severity of the depletion in the patients by comparison not only to normal controls but also to patients with mtDNA disorders. Despite the severity of the depletion, in situ hybridization using two mtDNA transcripts revealed a normal steady‐state level of transcription. Such compensation provides clues to the striking contrast between the severity of mtDNA depletion and the late onset and slowly progressive disease.