HEREDITARY SPHEROCYTOSIS ASSOCIATED WITH DELETION OF HUMAN ERYTHROCYTE ANKYRIN GENE ON CHROMOSOME-8
HEREDITARY SPHEROCYTOSIS ASSOCIATED WITH DELETION OF HUMAN ERYTHROCYTE ANKYRIN GENE ON CHROMOSOME-8
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DOI：
10.1038/345736a0
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发表时间：
1990-06-21
期刊：
影响因子：
64.8
通讯作者：
FORGET, BG
中科院分区：
文献类型：
--
作者：
LUX, SE;TSE, WT;FORGET, BG
遗传性球形细胞增多症是最常见的遗传性溶血性贫血之一。来自自声显性和隐性变种的HS红细胞都是幽灵蛋白缺乏的2，3，这与疾病的严重程度有关3。一些隐性HS患者具有血影蛋白α-2结构域的突变(S.L.M.等人，未发表的观察)，少数显性HS患者具有易被氧化的不稳定的β-血影蛋白4，这破坏了P4.1结合位点并减弱了血影蛋白-肌动蛋白相互作用5，6。然而，在大多数患者中，血影蛋白缺乏的原因尚不清楚。α-和β-Spectrin基因座分别位于第1-9号染色体和第14号染色体7-9号染色体上。HS的另一个基因座是位于第8号染色体(8p11)10-14短臂上的SPH2。这与红细胞膜蛋白的任何已知基因座都不对应，这些基因座包括蛋白质4.1(Ip36.2-p34)15、阴离子交换蛋白(Ae1，带3；17q21-QTER)16、17、糖蛋白C(2q14-q21)18和β-肌动蛋白(7-q22)19。人类红细胞骨架蛋白最近已被克隆20，21。我们现在发现，ankyrin基因定位于8pll.2染色体，两名患有严重HS和8号染色体杂合性缺失(del(8Xpl1-p21.1))的无关儿童的DNA中缺失一个拷贝。受影响的红细胞也缺乏粘蛋白。这些数据表明，SPH2基因座的HS是由缺陷或缺乏或强直蛋白引起的。
HEREDITARY spherocytosis (HS) is one of the most common hereditary haemolytic anaemias1. HS red cells from both autosound dominant and recessive variants are spectrin-deficient2,3, which correlates with the severity of the disease3. Some patients with recessive HS have a mutation in the spectrin α-2 domain (S.L.M. et al., unpublished observations), and a few dominant HS patients have an unstable β-spectrin that is easily oxidized4, which damages the protein 4.1 binding site and weakens spectrin-actin interactions5,6. In most patients, however, the cause of spectrin deficiency is unknown. The α- and β-spectrin loci are on chromosomes 1 and 14 respectively7–9. The only other genetic locus for HS isSPH2, on the short arm of chromosome 8 (8p11)10–14. This does not correspond to any of the known loci of genes for red cell membrane proteins including protein 4.1 (Ip36.2-p34)15, the anion exchange protein (AE1, band 3; 17q21-qter)16,17, glycophorin C (2ql4-q21)18, and β-actin (7pter-q22)19. Human erthrocyte ankyrin, which links β-spectrin to the anion exchange protein, has recently been cloned20,21. We now show that the ankyrin gene maps to chromosome 8pll.2, and that one copy is missing from DNA of two unrelated children with severe HS and heterozygous deletions of chromosome 8 (del(8Xpll-p21.1)). Affected red cells are also ankyrin-deficient. The data suggest that defects or deficiency or ankyrin are responsible for HS at theSPH2locus.