Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia

Alessia Nasca, Chiara Scotton, Irina Zaharieva, Marcella Neri, Rita Selvatici, Olafur Thor Magnusson, Aniko Gal, David Weaver, Rachele Rossi, Annarita Armaroli, Marika Pane, Rahul Phadke, Anna Sarkozy, Francesco Muntoni, Imelda Hughes, Antonella Cecconi, György Hajnóczky, Alice Donati, Eugenio Mercuri, Massimo ZevianiAlessandra Ferlini, Daniele Ghezzi

Research output: Contribution to journalArticlepeer-review


We report here the first families carrying recessive variants in the MSTO1 gene: compound heterozygous mutations were identified in two sisters and in an unrelated singleton case, who presented a multisystem complex phenotype mainly characterized by myopathy and cerebellar ataxia. Human MSTO1 is a poorly studied protein, suggested to have mitochondrial localization and to regulate morphology and distribution of mitochondria. As for other mutations affecting genes involved in mitochondrial dynamics, no biochemical defects typical of mitochondrial disorders were reported. Studies in patients’ fibroblasts revealed that MSTO1 protein levels were strongly reduced, the mitochondrial network was fragmented, and the fusion events among mitochondria were decreased, confirming the deleterious effect of the identified variants and the role of MSTO1 in modulating mitochondrial dynamics. We also found that MSTO1 is mainly a cytosolic protein. These findings indicate recessive mutations in MSTO1 as a new cause for inherited neuromuscular disorders with multisystem features.

Original languageEnglish
Pages (from-to)970-977
Number of pages8
JournalHuman Mutation
Issue number8
Publication statusPublished - Aug 1 2017


  • ataxia
  • mitochondrial dynamics
  • MSTO1
  • myopathy
  • skeletal abnormalities

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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