Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome
Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome
复制标题
DOI：
10.1182/blood-2010-12-326645
复制
发表时间：
2011-11-10
期刊：
影响因子：
20.3
通讯作者：
Bruce, Lesley J.
中科院分区：
文献类型：
--
作者：
Flatt, Joanna F.;Guizouarn, Helene;Bruce, Lesley J.
遗传性口细胞病是一系列显性遗传性溶血性贫血，其中红细胞膜对单价阳离子的渗透性病理性增加。在转运蛋白基因RHAG和SLC 4A 1中发现了某些形式的遗传性口细胞增多症的致病突变。葡萄糖转运蛋白1（glucose transporter 1，GT 1）缺乏综合征（glucose transporter 1，GT 1 deficiency syndrome，GT 1 DS）是由编码GT 1的SLC 2A 1突变引起的。Glut 1是哺乳动物血脑屏障中主要的葡萄糖转运蛋白，而Glut 1DS表现为一系列神经系统症状。我们以前曾报道过2例口蛋白缺乏性冷冻水胞症（sdCHC），这是一种罕见的口细胞增多症，与冷诱导的阳离子渗漏、溶血性贫血和肝脾肿大有关，但也与白内障、癫痫发作、智力低下和运动障碍有关。我们现在表明，sdCHC与SLC 2A 1突变，导致葡萄糖转运和阳离子泄漏的损失，如在非洲爪蟾卵母细胞中的表达研究所示。基于一个三维模型，我们提出了潜在的机制，潜在的表型的2个突变发现。我们调查了气孔蛋白在红细胞生成过程中的损失，发现这发生在网织红细胞成熟，并涉及内吞作用。比较和讨论了阵发性运动诱发的运动障碍和sdCHC表型的分子基础。（血。2011; 118（19）：5267-5277）
The hereditary stomatocytoses are a series of dominantly inherited hemolytic anemias in which the permeability of the erythrocyte membrane to monovalent cations is pathologically increased. The causative mutations for some forms of hereditary stomatocytosis have been found in the transporter protein genes, RHAG and SLC4A1. Glucose transporter 1 (glut1) deficiency syndromes (glut1DSs) result from mutations in SLC2A1, encoding glut1. Glut1 is the main glucose transporter in the mammalian blood-brain barrier, and glut1DSs are manifested by an array of neurologic symptoms. We have previously reported 2 cases of stomatin-deficient cryohydrocytosis (sdCHC), a rare form of stomatocytosis associated with a cold-induced cation leak, hemolytic anemia, and hepatosplenomegaly but also with cataracts, seizures, mental retardation, and movement disorder. We now show that sdCHC is associated with mutations in SLC2A1 that cause both loss of glucose transport and a cation leak, as shown by expression studies in Xenopus oocytes. On the basis of a 3-dimensional model of glut1, we propose potential mechanisms underlying the phenotypes of the 2 mutations found. We investigated the loss of stomatin during erythropoiesis and find this occurs during reticulocyte maturation and involves endocytosis. The molecular basis of the glut1DS, paroxysmal exercise-induced dyskinesia, and sdCHC phenotypes are compared and discussed. (Blood. 2011; 118(19): 5267-5277)