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Combined OXPHOS complex I and IV defect, due to mutated complex I assembly factor C20ORF7

2011; Springer Science+Business Media; Volume: 35; Issue: 1 Linguagem: Inglês

10.1007/s10545-011-9348-y

1573-2665

Ann Saada, Simon Edvardson, Avraham Shaag, Wendy K. Chung, Reeval Segel, Chaya Miller, Chaim Jalas, Orly Elpeleg,

ATP Synthase and ATPases Research

Abstract Defects of the mitochondrial oxidative phosphorylation (OXPHOS) system are frequent causes of neurological disorders in children. Linkage analysis and DNA sequencing identified a new founder p.G250V substitution in the C20ORF7 complex I chaperone in five Ashkenazi Jewish patients from two families with a combined OXPHOS complex I and IV defect presenting with Leigh's syndrome in infancy. Complementation with the wild type gene restored complex I, but only partially complex IV activity. Although the pathogenic mechanism remains elusive, a C20ORF7 defect should be considered not only in isolated complex I deficiency, but also in combination with decreased complex IV. Given the significant 1:290 carrier rate for the p.G250V mutation among Ashkenazi Jews, this mutation should be screened in all Ashkenazi patients with Leigh's syndrome prior to muscle biopsy.