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

• DOI: 10.1038/ng.378
• Publication Date: 2009-05-24T17:10:55Z
• Authors: Daniele Ghezzi; Paola Goffrini; Graziella Uziel; Rita Horvath; Thomas Klopstock; Hanns Lochmüller; Pio D'Adamo; Paolo Gasparini; Tim M Strom; Holger Prokisch; Federica Invernizzi; Ileana Ferrero; Massimo Zeviani
• Keywords: Iron-Sulfur Proteins; 0301 basic medicine; Genetic Complementation Test; Genetic Complementation Test; Humans; Infant; Iron-Sulfur Proteins; Leukoencephalopathies; Protein Subunits; Proteins; Sequence Deletion; Succinate Dehydrogenase; Yeasts; Mutation; 610; Infant; Proteins; Flavoprotein gene; mutations; paraganglioma; deficiency; succinate; Leukoencephalopathies; genetics; Leukoencephalopathie; Succinate Dehydrogenase; Protein Subunits; 03 medical and health sciences; Leukoencephalopathies; Yeasts; Mutation; Humans; genetics; Sequence Deletion

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.