Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1.
Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1.
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阵发性运动引起的运动障碍和癫痫症是由于SLC2A1中的突变引起的，编码了葡萄糖转运蛋白Glut1。
DOI：
10.1093/brain/awn113
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发表时间：
2008-07
期刊：
影响因子：
14.5
通讯作者：
Paesschen, WimVan
中科院分区：
文献类型：
--
作者：
Suls, Arvid;Dedeken, Peter;Goffin, Karolien;Van Esch, Hilde;Dupont, Patrick;Cassiman, David;Kempfle, Judith;Wuttke, Thomas V.;Weber, Yvonne;Lerche, Holger;Afawi, Zaid;Vandenberghe, Wim;Korczyn, Amos D.;Berkovic, Samuel F.;Ekstein, Dana;Kivity, Sara;Ryvlin, Philippe;Claes, Lieve R. F.;Deprez, Liesbet;Maljevic, Snezana;Vargas, Alberto;Van Dyck, Tine;Goossens, Dirk;Del-Favero, Jurgen;Van Laere, Koen;De Jonghe, Peter;Paesschen, WimVan
阵发性运动诱发的运动障碍（PED）可以单独发生或与癫痫相关，但其遗传原因和病理生理机制仍知之甚少。我们对一个同时患有PED和癫痫的五代家庭（n = 39）进行了临床评估和遗传分析，表明这种组合代表了一个临床实体。基于全基因组连锁分析，我们筛选了SLC 2A 1，编码血脑屏障葡萄糖转运蛋白GLUT 1，并确定了杂合错义和移码突变，在这个和其他三个具有相似表型的核心家族中分离。PED的特征是舞蹈徐动症、肌张力障碍或两者兼有，主要影响腿部。癫痫发作类型以原发全身型为主。患者的CSF/血糖比值中位数为0.52（正常>0.60），在非洲爪蟾卵母细胞中测定的突变转运蛋白与野生型相比葡萄糖摄取减少，证实了这些突变的致病作用。功能成像研究表明，PED病理生理学中皮质纹状体通路和癫痫发作病理生理学中额叶皮质的葡萄糖代谢发生改变。三名患者成功地用生酮饮食治疗。总之，合并发生的PED和癫痫可能是由于常染色体显性杂合子SLC 2A 1突变，扩大了与GLUT 1缺乏相关的表型谱，并为这种临床综合征提供了潜在的新治疗选择。
Paroxysmal exercise-induced dyskinesia (PED) can occur in isolation or in association with epilepsy, but the genetic causes and pathophysiological mechanisms are still poorly understood. We performed a clinical evaluation and genetic analysis in a five-generation family with co-occurrence of PED and epilepsy (n = 39), suggesting that this combination represents a clinical entity. Based on a whole genome linkage analysis we screened SLC2A1, encoding the glucose transporter of the blood-brain-barrier, GLUT1 and identified heterozygous missense and frameshift mutations segregating in this and three other nuclear families with a similar phenotype. PED was characterized by choreoathetosis, dystonia or both, affecting mainly the legs. Predominant epileptic seizure types were primary generalized. A median CSF/blood glucose ratio of 0.52 (normal >0.60) in the patients and a reduced glucose uptake by mutated transporters compared with the wild-type as determined in Xenopus oocytes confirmed a pathogenic role of these mutations. Functional imaging studies implicated alterations in glucose metabolism in the corticostriate pathways in the pathophysiology of PED and in the frontal lobe cortex in the pathophysiology of epileptic seizures. Three patients were successfully treated with a ketogenic diet. In conclusion, co-occurring PED and epilepsy can be due to autosomal dominant heterozygous SLC2A1 mutations, expanding the phenotypic spectrum associated with GLUT1 deficiency and providing a potential new treatment option for this clinical syndrome.
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影响因子：
2.9
作者：
Klepper, J;Salas-Burgos, A;Fischbarg, J
通讯作者：
Fischbarg, J
DOI：
10.1016/j.plefa.2003.07.004
发表时间：
2004-03-01
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3
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Refetoff, S
影响因子：
9.9
作者：
Deprez, L.;Peeters, K.;De Jonghe, P.
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