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