Abstract
Mutations in mitochondrial ATP synthase 6 (MT-ATP6) are a frequent cause of NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) or Leigh syndromes, especially a point mutation at nucleotide position 8993. M.8969G>A is a rare MT-ATP6 mutation, previously reported only in three individuals, causing multisystem disorders with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia or IgA nephropathy. We present two siblings with the m.8969G>A mutation and a novel, substantially milder phenotype with lactic acidosis, poor growth, and intellectual disability. Our findings expand the phenotypic spectrum and show that mtDNA mutations should be taken account also with milder, stable phenotypes.
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Acknowledgements
The authors would like to thank the family for participation in the study. We acknowledge Brendan Battersby for discussions, and the Finnish Institute for Molecular Medicine (FIMM) for DNA sequencing services. We wish to thank the following funding sources for support: Foundation for Pediatric Research (PI), the special governmental subsidy for health sciences research of the Helsinki University Hospital. (PI and TL), University of Helsinki (CJC and AS), Swiss National Foundation and Novartis Foundation (CJB), Sigrid Jusélius Foundation, Academy of Finland, Jane and Aatos Erkko Foundation (AS).
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Isohanni, P., Carroll, C.J., Jackson, C.B. et al. Defective mitochondrial ATPase due to rare mtDNA m.8969G>A mutation—causing lactic acidosis, intellectual disability, and poor growth. Neurogenetics 19, 49–53 (2018). https://doi.org/10.1007/s10048-018-0537-9
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DOI: https://doi.org/10.1007/s10048-018-0537-9