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Novel homozygous TSFM pathogenic variant associated with encephalocardiomyopathy with sensorineural hearing loss and peculiar neuroradiologic findings

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Abstract

TSFM is a nuclear gene encoding the elongation factor Ts (EFTs), an essential component of mitochondrial translational machinery. Impaired mitochondrial translation is responsible for neurodegenerative disorders characterized by multiple respiratory chain complex defects, multisystemic involvement, and neuroradiological features of Leigh-like syndrome. With the use of a next-generation sequencing (NGS)–based multigene panel for mitochondrial disorders, we identified the novel TSFM homozygous variant c.547G>A (p.Gly183Ser) in a 5-year-old boy with infantile early onset encephalocardiomyopathy, sensorineural hearing loss, and peculiar partially reversible neuroimaging features. Our findings expand the phenotypic spectrum of TSFM-related encephalopathy, offering new insights into the natural history of brain involvement and suggesting that TSFM should be investigated in pediatric mitochondrial disorders with distinctive neurologic and cardiac involvement.

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Author notes

  1. Marcello Scala and Giorgia Brigati contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Neurology and Muscular Disorders, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini, 5, 16147, Genoa, Italy

    Marcello Scala, Chiara Fiorillo & Carlo Minetti

  2. University of Genoa, Genoa, Italy

    Marcello Scala, Chiara Fiorillo & Carlo Minetti

  3. Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Giorgia Brigati, Marina Pedemonte & Claudio Bruno

  4. Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris, Calambrone, Pisa, Italy

    Claudia Nesti, Anna Rubegni & F. M. Santorelli

  5. Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Mariasavina Severino

  6. Department of Pediatric Cardiology, IRCCS Istituto Giannina Gaslini, Genoa, Italy

    Maria Derchi

Authors
  1. Marcello Scala
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  2. Giorgia Brigati
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  3. Chiara Fiorillo
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  5. Anna Rubegni
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  6. Marina Pedemonte
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  7. Claudio Bruno
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  8. Mariasavina Severino
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  9. Maria Derchi
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  10. Carlo Minetti
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  11. F. M. Santorelli
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Corresponding author

Correspondence to Chiara Fiorillo.

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Tissue and blood samples were obtained for diagnostic purposes after ethical approval from the Ethic Committee of our Institution and written informed consent from the patient’s mother.

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Scala, M., Brigati, G., Fiorillo, C. et al. Novel homozygous TSFM pathogenic variant associated with encephalocardiomyopathy with sensorineural hearing loss and peculiar neuroradiologic findings. Neurogenetics 20, 165–172 (2019). https://doi.org/10.1007/s10048-019-00582-5

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  • DOI: https://doi.org/10.1007/s10048-019-00582-5

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