Homozygous mutation, p.Pro304His, in IDH3A, encoding isocitrate dehydrogenase subunit is associated with severe encephalopathy in infancy
详细信息 查看全文
- 作者：Aviva Fattal-Valevski ; Hila Eliyahu ; NItai D. Fraenkel ; Ganit Elmaliach…
- 关键词：Mitochondrial encephalopathy ; Tricarboxylic acid cycle ; Epilepsy
- 刊名：neurogenetics
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：18
- 期：1
- 页码：57-61
- 全文大小：
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Neurosciences; Human Genetics; Molecular Medicine;
- 出版者：Springer Berlin Heidelberg
- ISSN：1364-6753
- 卷排序：18
文摘
Mitochondrial encephalopathies are a heterogeneous group of disorders which generally carries a grave prognosis. Using exome sequencing, we identified a homozygous mutation, Pro-304-His in the IDH3A gene, in a patient suffering from infantile encephalopathy with peripheral and autonomic nervous system involvement. Mammalian isocitrate dehydrogenase (IDH) 3 is a heterotetramer of 2alfa, 1beta, and 1gamma subunits, and IDH3A encodes the alfa subunit of the mitochondrial NAD+-dependent IDH. Here we show that in contrast to wild-type human IDH3A, the human IDH3A which harbor the p.Pro304His mutation does not complement the yeast Δidh1/Δidh2 growth defect on ethanol-acetate. We therefore propose that homozygosity for the p.Pro304His mutation is deleterious for mitochondrial NAD+-specific IDH3A activity in human. IDH3A now joins the list of TCA cycle-related proteins, which includes ACO2, DLD, SLC25A19, FH, and succinate dehydrogenase subunits, all associated with neurological disorders.