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您的检索式：作者名="Dominique Steschenko"
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| 1 | Lafora progressive myoclonus epilepsy: NHLRC1 mutations affect glycogen metabolism显示文摘Lafora disease is a fatal autosomal recessive formof progressive myoclonus epilepsy. Patients manifest myoclonus and tonic–clonic seizures, visual hallucinations, intellectual, and progressive neurologic deterioration beginning in adolescence.The two genes known to be involved in Lafora disease are EPM2 A and NHLRC1(EPM2B). The EPM2 A gene encodes laforin,a dual-specificity protein phosphatase, and the NHLRC1 gene encodes malin, an E3-ubiquitin ligase. The two proteins interact with each other and, as a complex, are thought to regulate glycogen synthesis. Here, we report three Lafora families with two novel pathogenic mutations(C46Y and L261P) and two recurrent mutations(P69A and D146N) in NHLRC1. Investigation of their functional consequences in cultured mammalian cells revealed that malin C46 Y, malin P69 A, malin D146 N, and malin L261 P mutants failed to downregulate the level of R5/PTG, a regulatory subunit of protein phosphatase 1 involved in glycogen synthesis. Abnormal accumulation of intracellular glycogen was observed with all malin mutants, reminiscent of the polyglucosan inclusions(Lafora bodies) present in patients with Lafora disease. | Philippe Couarch Santiago Vernia Isabelle Gourfinkel-An Ga tan Lesca Svetlana Gataullina Estelle Fedirko Oriane Trouillard Christel Depienne Olivier Dulac Dominique Steschenko Eric Leguern Pascual Sanz Stéphanie Baulac | 2015 | 世界最新医学信息文摘2015，15，5： | 0 |
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