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

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

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00860

DOI=10.3389/fgene.2020.00860

ISSN=1664-8021

ABSTRACT=<p>Biallelic <italic>TYMP</italic> variants result in the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a juvenile-onset disorder with progressive course and fatal outcome. Milder late-onset (&gt;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 <italic>TYMP</italic> 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 <italic>TYMP</italic> is recommended in adult patients with muscle mtDNA instability, even in the absence of cardinal MNGIE features.</p>