mtDNA deletion in a patient with symptoms of mitochondrial cytopathy but without ragged red fibers

Biochem Mol Med. 1995 Oct;56(1):26-30. doi: 10.1006/bmme.1995.1052.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Southern
  • Child
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics*
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / genetics
  • Female
  • Fibroblasts / chemistry
  • Humans
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / metabolism
  • Mitochondrial Myopathies / pathology
  • Molecular Sequence Data
  • Muscle Fibers, Skeletal / chemistry
  • Muscle Fibers, Skeletal / pathology
  • Nucleic Acid Conformation
  • Point Mutation
  • Polymerase Chain Reaction
  • RNA, Ribosomal / genetics
  • Sequence Deletion*

Substances

  • DNA, Mitochondrial
  • DNA, Ribosomal
  • RNA, Ribosomal
  • RNA, ribosomal, 12S