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.

SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy / D. Ghezzi, P. Goffrini, G. Uziel, R. Horvath, T. Klopstock, H. Lochmuller, P. D'Adamo, P. Gasparini, T.M. Strom, H. Prokisch, F. Invernizzi, I. Ferrero, M. Zeviani. - In: NATURE GENETICS. - ISSN 1061-4036. - 41:6(2009), pp. 654-656. [10.1038/ng.378]

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

Ghezzi D.;Gasparini P.;Ferrero I.;
2009

Abstract

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.
Flavoprotein gene; mutations; paraganglioma; deficiency; succinate
Settore MED/03 - Genetica Medica
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/781134
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