Relative frequency of known causes of multiple mtDNA deletions: Two novel POLG mutations

Mariana Ferreira, Teresinha Evangelista, Lígia S. Almeida, João Martins, Maria Carmo Macario, Esmeralda Martins, Ana Moleirinho, Luísa Azevedo, Laura Vilarinho, Filippo M. Santorelli

Research output: Contribution to journalArticlepeer-review


Diseases affecting mtDNA stability, termed nuclear-mitochondrial intergenomic communication disorders, are caused by a primary nuclear gene defect resulting in multiple mtDNA deletions.The aim of this study was to estimate the frequency of known etiologies and the spectrum of mutations in a cohort of 21 patients harboring multiple mtDNA deletions in skeletal muscle.We showed that 10 cases (48%) display mutations in POLG, including eight previously reported variants and two novel mutations (namely, p.Trp585X and p.Arg1081Gln). The novel mutations affect evolutionary conserved residues and were absent in a large set of control chromosomes. These findings expand the array of mutations associated with multiple rearranged mtDNA attributed to mutations in POLG. The relatively high diagnostic yield (about one in two cases) supports the notion that it is recommended to test POLG routinely in diagnostic laboratories whenever multiple mtDNA deletions are present, regardless of the age of onset of patients and their clinical phenotype.

Original languageEnglish
Pages (from-to)483-488
Number of pages6
JournalNeuromuscular Disorders
Issue number7
Publication statusPublished - Jul 2011


  • Cancer
  • Mitochondrial disorders
  • MtDNA
  • Multiple deletions
  • Oxidative metabolism
  • POLG

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology


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