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

  • Claudia NestiEmail author
  • Anna Rubegni
  • Deborah Tolomeo
  • Jacopo Baldacci
  • Denise Cassandrini
  • Francesca D’Amore
  • Filippo M. SantorelliEmail author
Brief Communication


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.


mtDNA mutation Heteroplasmy tRNATrp Multisystem disorder Massive parallel sequencing 



We are indebted to Dr. Catherine J. Wrenn for expert editing of the manuscript and critical advice.

Funding information

This work was partially supported by grant MITONEXT (to FMS) and Ricerca Corrente 5x1000 2018 from the Italian Ministry of Health.

Compliance with ethical standards

All the procedures complied with the Helsinki Declaration of 1975. This study was approved by our institutional ethics committee.

Supplementary material

10072_2019_3864_MOESM1_ESM.docx (12 kb)
ESM 1 (DOCX 12 kb)


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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Molecular Medicine for Neurodegenerative and Neuromuscular Diseases UnitIRCCS Stella Maris FoundationPisaItaly
  2. 2.Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly

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