title: mtDNA deletion in a patient with symptoms of mitochondrial cytopathy but without ragged red fibers.
abstract: We describe a heteroplasmic 4237-bp mitochondrial DNA (mtDNA) deletion in an 11-year-old girl who has suffered from progressive illness since birth. Her clinical features include global developmental delay with regression, brainstem dysfunction, lactic acidosis, and a history of pancytopenia and failure to thrive. The deletion spanned nt 9498 to nt 13734 and was flanked by a 12-bp direct repeat. Southern blot analysis also revealed an altered ApaI restriction site caused by a G --> A nucleotide substitution at nt 1462 in the 12S rRNA gene. This homoplasmic nucleotide change was presumed to be a mtDNA nucleotide variant. No abnormalities of mitochondrial ultrastructure or distribution were observed, although mild deficiencies were noted for complexes IV, II + III, and I of the mitochondrial respiratory chain. The absence of ragged red fibers and COX-negative fibers in this patient shows that mtDNA deletions do not always result in these classical hallmarks of mitochondrial cytopathies.
authors.affiliation: Murdoch Institute, Royal Children's Hospital, Melbourne, Victoria, Australia.
authors.forename: R B
authors.initials: RB
authors.lastname: Blok
authors.forename: D R
authors.initials: DR
authors.lastname: Thorburn
authors.forename: D M
authors.initials: DM
authors.lastname: Danks
authors.forename: H H
authors.initials: HH
authors.lastname: Dahl
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D002648:Child; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000473:pathology; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012335:RNA, Ribosomal / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D004275:DNA, Ribosomal; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S