Erschienen in:
01.01.2012 | Original Article
Combined OXPHOS complex I and IV defect, due to mutated complex I assembly factor C20ORF7
verfasst von:
Ann Saada, Shimon Edvardson, Avraham Shaag, Wendy K. Chung, Reeval Segel, Chaya Miller, Chaim Jalas, Orly Elpeleg
Erschienen in:
Journal of Inherited Metabolic Disease
|
Ausgabe 1/2012
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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.