title: Combined OXPHOS complex I and IV defect, due to mutated complex I assembly factor C20ORF7.
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.
authors: Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, POB 1200, 91120 Jerusalem, Israel. annsr@hadassah.org.il
authors: Ann
authors: A
authors: Saada
authors: Shimon
authors: S
authors: Edvardson
authors: Avraham
authors: A
authors: Shaag
authors: Wendy K
authors: WK
authors: Chung
authors: Reeval
authors: R
authors: Segel
authors: Chaya
authors: C
authors: Miller
authors: Chaim
authors: C
authors: Jalas
authors: Orly
authors: O
authors: Elpeleg
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