Mutation in the COX4I1 gene is associated with short stature, poor weight gain and increased chromosomal breaks, simulating Fanconi anemia
| Autor: | Ann Saada, Sarah Amro, Liza Douiev, Chaya Miller, Asaf Ta-Shma, Maher Shahrour, Orly Elpeleg, Bassam Abu-Libdeh |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mutation Mitochondrial disease Biology medicine.disease medicine.disease_cause Molecular biology Article 03 medical and health sciences COX4I1 030104 developmental biology 0302 clinical medicine Mitochondrial respiratory chain Fanconi anemia Genetics medicine Cancer research biology.protein Cytochrome c oxidase Gene 030217 neurology & neurosurgery Genetics (clinical) Exome sequencing |
| Zdroj: | European Journal of Human Genetics. 25:1142-1146 |
| ISSN: | 1476-5438 1018-4813 |
| Popis: | We describe a novel autosomal recessive form of mitochondrial disease in a child with short stature, poor weight gain, and mild dysmorphic features with highly suspected Fanconi anemia due to a mutation in COX4I1 gene. Whole Exome Sequencing was performed then followed by Sanger confirmation, identified a K101N mutation in COX4I1, segregating with the disease. This nuclear gene encodes the common isoform of cytochrome c oxidase (COX) subunit 4 (COX 4-1), an integral regulatory part of COX (respiratory chain complex IV) the terminal electron acceptor of the mitochondrial respiratory chain. The patient’s fibroblasts disclosed decreased COX activity, impaired ATP production, elevated ROS production, decreased expression of COX4I1 mRNA and undetectable (COX4) protein. COX activity and ATP production were restored by lentiviral transfection with the wild-type gene. Our results demonstrate the first human mutation in the COX4I1 gene linked to diseases and confirm its role in the pathogenesis. Thus COX4I1 mutations should be considered in any patient with features suggestive of this diagnosis. |
| Databáze: | OpenAIRE |
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