A novel homozygous MSTO1 mutation in Ashkenazi Jewish siblings with ataxia and myopathy

Alessia Nasca, Ivano Di Meo, Yakov Fellig, Ann Saada, Orly Elpeleg, Daniele Ghezzi, Shimon Edvardson

Research output: Contribution to journalArticlepeer-review


MSTO1 is a cytoplasmic protein that modulates mitochondrial dynamics by promoting mitochondrial fusion. Mutations in the MSTO1 gene are responsible for an extremely rare condition characterized by early-onset myopathy and cerebellar ataxia. We report here two siblings from a large Ashkenazi Jewish family, presenting with a progressive neuromuscular disease characterized by ataxia and myopathy. By whole exome sequencing, we found a novel homozygous missense mutation (c.1403T>A, p.Leu468Gln) in MSTO1. Studies performed on fibroblasts from the index patient demonstrated the pathogenic role of the identified variant; we found that MSTO1 protein level was reduced and that mitochondrial network was fragmented or formed enlarged structures. Moreover, patient’s cells showed reduced mitochondrial DNA amount. Our report confirms that MSTO1 mutations are typically recessive, and associated with clinical phenotypes characterized by early-onset muscle impairment and ataxia, often with upper motor neuron signs and varied cognitive impairment.

Original languageEnglish
Pages (from-to)835-840
Number of pages6
JournalJournal of Human Genetics
Issue number8
Publication statusPublished - Aug 2021

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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