title: Late-onset mitochondrial DNA depletion: DNA copy number, multiple deletions, and compensation.
abstract: 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.
authors.affiliation: INSERM UR523, Institut de Myologie, H pital de La Salpêtrière, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Barthélémy
authors.forename: H
authors.initials: H
authors.lastname: Ogier de Baulny
authors.forename: J
authors.initials: J
authors.lastname: Diaz
authors.forename: M A
authors.initials: MA
authors.lastname: Cheval
authors.forename: P
authors.initials: P
authors.lastname: Frachon
authors.forename: N
authors.initials: N
authors.lastname: Romero
authors.forename: F
authors.initials: F
authors.lastname: Goutieres
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: A
authors.initials: A
authors.lastname: Lombès
mesh_terms: D017668:Age of Onset; D015139:Blotting, Southern; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D017403:In Situ Hybridization; D007625:Kearns-Sayre Syndrome / Q000235:genetics* / Q000473:pathology; D008297:Male; D009132:Muscles / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial