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Novel recessive mutations in MSTO1 cause cerebellar atrophy with pigmentary retinopathy


Misato 1, mitochondrial distribution and morphology regulator (encoded by the MSTO1 gene), is involved in mitochondrial distribution and morphology. Recently, MSTO1 mutations have been shown to cause clinical manifestations suggestive of mitochondrial dysfunction, such as muscle weakness, short stature, motor developmental delay, and cerebellar atrophy. Both autosomal dominant and recessive modes of inheritance have been suggested. We performed whole-exome sequencing in two unrelated patients showing cerebellar atrophy, intellectual disability, and pigmentary retinopathy. Three novel mutations were identified: c.836 G > A (p.Arg279His), c.1099-1 G > A (p.Val367Trpfs*2), and c.79 C > T (p.Gln27*). Both patients had compound heterozygous mutations with a combination of protein-truncation mutation and missense mutation, the latter shared by them both. This survey of two patients with recessive and novel MSTO1 mutations provides additional clinical and genetic information on the pathogenicity of MSTO1 in humans.

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We thank the individuals and their families for their participation in this study. We also thank Nobuko Watanabe and Mai Sato for technical assistance. We are also thanks Edanz Group ( for editing a draft of this manuscript. This work was supported by grants from Research on Measures for Intractable Diseases, Comprehensive Research on Disability Health and Welfare, the Strategic Research Program for Brain Science (SRPBS), the Practical Research Project for Rare/Intractable Diseases, the Initiative on Rare and Undiagnosed Diseases from the Japan Agency for Medical Research and Development, a Grant-in-Aid for Scientific Research on Innovative Areas (Transcription Cycle) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Grants-in-Aid for Scientific Research (A and B), Grant-in-Aid for Young Scientists (B), Challenging Exploratory Research from the Japan Society for the Promotion of Science, the fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the Japan Science and Technology Agency, grants from the Ministry of Health, Labor and Welfare, and the Takeda Science Foundation.

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Correspondence to Naomichi Matsumoto.

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Iwama, K., Takaori, T., Fukushima, A. et al. Novel recessive mutations in MSTO1 cause cerebellar atrophy with pigmentary retinopathy. J Hum Genet 63, 263–270 (2018).

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