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Combined OXPHOS complex I and IV defect, due to mutated complex I assembly factor C20ORF7
Author(s) -
Saada Ann,
Edvardson Shimon,
Shaag Avraham,
Chung Wendy K.,
Segel Reeval,
Miller Chaya,
Jalas Chaim,
Elpeleg Orly
Publication year - 2012
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-011-9348-y
Subject(s) - complementation , genetics , mitochondrial dna , mutation , gene , oxidative phosphorylation , biology , medicine , biochemistry , phenotype
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.