Complex multisystem phenotype associated with the mitochondrial DNA m.5522G>A mutation

Claudia Nesti, Anna Rubegni, Deborah Tolomeo, Jacopo Baldacci, Denise Cassandrini, Francesca D’Amore, Filippo M. Santorelli

Research output: Contribution to journalArticlepeer-review


Mitochondrial tRNAs are responsible for more than half of pathogenic point mutations in the mitochondrial genome (mtDNA). Different mutations give rise to widely differing phenotypes, ranging from isolated organ-specific diseases to multisystem conditions. Herein, we report a 40-year-old woman presenting with a complex multisystem phenotype including sensorineural hearing loss, retinopathy, severe dilated cardiomyopathy, non-insulin dependent diabetes mellitus, and renal failure. Sequence analysis of mtDNA identified the m.5522G>A mutation in MT-TW, the gene encoding mitochondrial tRNA for tryptophan. The heteroplasmic variant, thus far described once, was almost exclusively confined to skeletal muscle tissue, as shown by massive parallel sequencing and corroborated by an ad hoc designed PCR-based strategy. This patient, presenting a severe, multisystem involvement apparently sparing the brain, contributes to the genetic heterogeneity of mitochondrial diseases caused by mutations in mitochondrial tRNAs.

Original languageEnglish
Pages (from-to)1705-1708
Number of pages4
JournalNeurological Sciences
Issue number8
Publication statusPublished - Aug 1 2019


  • Heteroplasmy
  • Massive parallel sequencing
  • mtDNA mutation
  • Multisystem disorder
  • tRNA

ASJC Scopus subject areas

  • Dermatology
  • Clinical Neurology
  • Psychiatry and Mental health


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