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A case of PDH-E1α mosaicism in a male patient with severe metabolic lactic acidosis

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Journal of Inherited Metabolic Disease

Abstract

We have characterized a novel mutation in a male patient that affects the coding sequence of PDH-E1α gene and changes arginine-141 to a leucine. This nucleotide substitution was found in about 75% of the studied DNA (fibroblasts, liver and muscle), a scenario that would indicate a case of E1α mosaicism in a male patient. When the mutant E1α protein was expressed in human skin fibroblasts with zero endogenous pyruvate dehydrogenase complex activity and E1α protein expression, no significant restoration of activity was recorded, in contrast to the wild-type cDNA, even though both wild-type and mutant protein levels were comparable. We concluded that the R141L mutation is a severe one and that it must have occurred in one of the E1α alleles during early embryogenesis.

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Authors and Affiliations

  1. Metabolism Research Programme, Research Institute,Hospital for Sick Children and Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada

    A. Seyda & B. H. Robinson

  2. Cancer Cytogenetics Laboratory, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada

    K. Chun

  3. Department of Paediatrics, Division of Genetics, University of California, San Francisco, California, USA

    S. Packman

Authors
  1. A. Seyda
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  2. K. Chun
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  3. S. Packman
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  4. B. H. Robinson
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Seyda, A., Chun, K., Packman, S. et al. A case of PDH-E1α mosaicism in a male patient with severe metabolic lactic acidosis. J Inherit Metab Dis 24, 551–559 (2001). https://doi.org/10.1023/A:1012463726810

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