Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia.
Magnusson, Olafur Thor
John Wiley & Sons Inc.
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Nasca, A., Scotton, C., Zaharieva, I., Neri, M., Selvatici, R., Magnusson, O. T., Gal, A., et al. (2017). Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia.. Human Mutation, 38 (8), 970-977. https://doi.org/10.1002/humu.23262
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.
MSTO1, ataxia, mitochondrial dynamics, myopathy, skeletal abnormalities, Ataxia, Cell Cycle Proteins, Child, Child, Preschool, Cytoskeletal Proteins, Female, Humans, Infant, Infant, Newborn, Mitochondrial Dynamics, Muscular Diseases, Mutation
Contract grant sponsors: EU NeurOmics (project N. 2012‐305121‐2); the European Community's Seventh Framework Programme (FP7/2007‐2013); Regione Emilia Romagna; the Telethon (grant GGP15041); the Pierfranco and Luisa Mariani Foundation; the MRC‐QQR (2015‐20120); the ERC advanced grant (FP7‐322424); the NRJ‐Institut de France grant; Telethon Network of Genetic Biobanks (grant GTB12001J); MRC Neuromuscular Centre (for the Biobank); Muscular Dystrophy UK; National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
European Commission FP7 ERC Advanced Investigator Grants (AIG) (322424)
EC FP7 CP (305121)
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External DOI: https://doi.org/10.1002/humu.23262
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266583
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/