Genotype and phenotype analyses in 136 patients with single large-scale mitochondrial DNA deletions

J Hum Genet. 2008;53(7):598. doi: 10.1007/s10038-008-0289-8. Epub 2008 Apr 15.

Abstract

We examined 136 patients with mitochondrial DNA (mtDNA) deletion. Clinical diagnoses included chronic progressive external ophthalmoplegia (94 patients); Kearns-Sayre syndrome (KSS; 33 patients); Pearson's marrow-pancreas syndrome (six patients); and Leigh syndrome, Reye-like syndrome, and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (one patient). The length and location of deletion were highly variable. Only one patient had deletion within the so-called shorter arc between the two origins of mtDNA replication. The length of deletion and the number of deleted transfer ribonucleic acid (tRNAs) showed a significant relationship with age at onset. Furthermore, KSS patients had longer and larger numbers of deleted tRNAs, which could be risk factors for the systemic involvement of single mtDNA deletion diseases. We found 81 patterns of deletion. Direct repeats of 4 bp or longer flanking the breakpoints were found in 96 patients (70.5%) and those of 10 bp or longer in 49 patients (36.0%). We found two other common deletions besides the most common deletion (34 patients: 25.0%): the 2,310-bp deletion from nt 12113 to nt 14421 (11 patients: 8.0%) and the 7,664-bp deletion from nt 6330 to nt 13993 (ten patients: 7.3%). These deletions had incomplete direct repeats longer than 13 bp with one base mismatch.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Base Sequence / genetics
  • Child
  • Child, Preschool
  • DNA, Mitochondrial / genetics*
  • Female
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mitochondria / genetics*
  • Mitochondrial Diseases / genetics
  • Phenotype*
  • Sequence Deletion / genetics*

Substances

  • DNA, Mitochondrial