Lack of the mitochondrial protein acylglycerol kinase causes sengers syndrome

Johannes A. Mayr, Tobias B. Haack, Elisabeth Graf, Franz A. Zimmermann, Thomas Wieland, Birgit Haberberger, Andrea Superti-Furga, Janbernd Kirschner, Beat Steinmann, Matthias R. Baumgartner, Isabella Moroni, Eleonora Lamantea, Massimo Zeviani, Richard J. Rodenburg, Jan Smeitink, Tim M. Strom, Thomas Meitinger, Wolfgang Sperl, Holger Prokisch

Research output: Contribution to journalArticle

Abstract

Exome sequencing of an individual with congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis, all typical symptoms of Sengers syndrome, discovered two nonsense mutations in the gene encoding mitochondrial acylglycerol kinase (AGK). Mutation screening of AGK in further individuals with congenital cataracts and cardiomyopathy identified numerous loss-of-function mutations in an additional eight families, confirming the causal nature of AGK deficiency in Sengers syndrome. The loss of AGK led to a decrease of the adenine nucleotide translocator in the inner mitochondrial membrane in muscle, consistent with a role of AGK in driving the assembly of the translocator as a result of its effects on phospholipid metabolism in mitochondria.

Original languageEnglish
Pages (from-to)314-320
Number of pages7
JournalAmerican Journal of Human Genetics
Volume90
Issue number2
DOIs
Publication statusPublished - Feb 10 2012

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Mayr, J. A., Haack, T. B., Graf, E., Zimmermann, F. A., Wieland, T., Haberberger, B., Superti-Furga, A., Kirschner, J., Steinmann, B., Baumgartner, M. R., Moroni, I., Lamantea, E., Zeviani, M., Rodenburg, R. J., Smeitink, J., Strom, T. M., Meitinger, T., Sperl, W., & Prokisch, H. (2012). Lack of the mitochondrial protein acylglycerol kinase causes sengers syndrome. American Journal of Human Genetics, 90(2), 314-320. https://doi.org/10.1016/j.ajhg.2011.12.005