Brief Communication abstract

Nature Genetics 41, 654 - 656 (2009)
Published online: 24 May 2009 | doi:10.1038/ng.378

SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy

Daniele Ghezzi1, Paola Goffrini2, Graziella Uziel3, Rita Horvath4,5, Thomas Klopstock5, Hanns Lochmüller5,6, Pio D'Adamo7, Paolo Gasparini7, Tim M Strom8, Holger Prokisch8, Federica Invernizzi1, Ileana Ferrero2 & Massimo Zeviani1


We report mutations in SDHAF1, encoding a new LYR-motif protein, in infantile leukoencephalopathy with defective succinate dehydrogenase (SDH, complex II). Disruption of the yeast homolog or expression of variants corresponding to human mutants caused SDH deficiency and failure of OXPHOS-dependent growth, whereas SDH activity and amount were restored in mutant fibroblasts proportionally with re-expression of the wild-type gene. SDHAF1 is the first bona fide SDH assembly factor reported in any organism.

  1. Unit of Molecular Neurogenetics–Pierfranco and Luisa Mariani Center for Study of Children's Mitochondrial Disorders, Foundation IRCCS Neurological Institute “C. Besta”, Milan, Italy.
  2. Department of Genetics, Anthropology, Evolution, University of Parma, Parma, Italy.
  3. Department of Child Neurology, Foundation IRCCS Neurological Institute “C. Besta”, Milan, Italy.
  4. Mitochondrial Research Group, Newcastle University, Newcastle upon Tyne, UK.
  5. Department of Neurology, Friedrich-Baur Institute, Ludwig-Maximilians University, Munich, Germany.
  6. Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK.
  7. Department of Medical Genetics, IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy.
  8. Institute of Human Genetics, Helmholtz Zentrum, Munich, Germany.

Correspondence to: Massimo Zeviani1 e-mail:


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