Mitochondrial A12308G polymorphism affects clinical features in patients with single mtDNA macrodeletion

Eur J Hum Genet. 2003 Nov;11(11):896-8. doi: 10.1038/sj.ejhg.5201056.


Mitochondrial (mt)DNA alterations cause cellular energy failure and respiratory chain dysfunction. Single large-scale rearrangements represent the most common mtDNA mutations and are responsible for very variable clinical manifestations. Here, we show an increased frequency of the A12308G substitution, a common polymorphism used to define the European mtDNA haplogroup U, in mitochondrial patients carrying mtDNA single macrodeletion. In this group of patients, A12308G substitution is associated with a higher relative risk of developing pigmentary retinal degeneration, short stature, dysphasia-dysarthria and cardiac conduction defects. MtDNA haplotype might modulate the clinical expression of mitochondrial encephalomyopathies due to mtDNA macrodeletions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • DNA, Mitochondrial / genetics*
  • Haplotypes
  • Humans
  • Mitochondria / genetics
  • Mitochondrial Encephalomyopathies / genetics
  • Mutation
  • Point Mutation
  • Polymorphism, Genetic*
  • Sequence Deletion


  • DNA, Mitochondrial