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

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 w...

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Bibliographic Details
Published in:Journal of inherited metabolic disease 2012, Vol.35 (1), p.125-131
Main Authors: Saada, Ann, Edvardson, Shimon, Shaag, Avraham, Chung, Wendy K., Segel, Reeval, Miller, Chaya, Jalas, Chaim, Elpeleg, Orly
Format: Article
Language:English
Subjects:
Biochemistry
Biological and medical sciences
Biopsy
Child
Child, Preschool
Electron Transport Complex I - genetics
Electron Transport Complex IV - genetics
Family Health
Female
Genetic Complementation Test
Human Genetics
Humans
Internal Medicine
Jews
Leigh Disease - genetics
Male
Medical genetics
Medical sciences
Medicine
Medicine & Public Health
Metabolic Diseases
Methyltransferases - genetics
Mitochondrial Diseases - genetics
Mitochondrial Proteins - genetics
Models, Genetic
Muscles - pathology
Original Article
Oxidative Phosphorylation
Pediatrics
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Summary: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.
ISSN:0141-8955
1573-2665
DOI:10.1007/s10545-011-9348-y