Frontiers in Genetics (Aug 2020)

TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

  • Dario Ronchi,
  • Dario Ronchi,
  • Leonardo Caporali,
  • Giulia Francesca Manenti,
  • Megi Meneri,
  • Susan Mohamed,
  • Andreina Bordoni,
  • Francesca Tagliavini,
  • Manuela Contin,
  • Manuela Contin,
  • Daniela Piga,
  • Monica Sciacco,
  • Cristina Saetti,
  • Cristina Saetti,
  • Valerio Carelli,
  • Valerio Carelli,
  • Giacomo Pietro Comi,
  • Giacomo Pietro Comi

DOI
https://doi.org/10.3389/fgene.2020.00860
Journal volume & issue
Vol. 11

Abstract

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Biallelic TYMP variants result in the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a juvenile-onset disorder with progressive course and fatal outcome. Milder late-onset (>40 years) form has been rarely described. Gene panel sequencing in a cohort of 60 patients featuring muscle accumulation of mitochondrial DNA (mtDNA) deletions detected TYMP defects in three subjects (5%), two of them with symptom onset in the fifth decade. One of the patients only displayed ptosis and ophthalmoparesis. Biochemical and molecular studies supported the diagnosis. Screening of TYMP is recommended in adult patients with muscle mtDNA instability, even in the absence of cardinal MNGIE features.

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