Molecular basis of hereditary persistence of fetal hemoglobin
Molecular basis of hereditary persistence of fetal hemoglobin
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DOI：
10.1111/j.1749-6632.1998.tb10460.x
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Forget, BG
中科院分区：
文献类型：
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作者：
Forget, BG
升高的胎儿血红蛋白（HbF）水平可以改善遗传-珠蛋白基因表达障碍的临床病程，如-地中海贫血和镰状心贫血。在一组称为遗传性胎儿血红蛋白持久性（HPFH）的疾病中，WP的γ -珠蛋白基因在成年红细胞中持续高水平表达。HPFH综合征的分子研究已经确定了γ -珠蛋白基因表达正常模式的几个重要调控元件。HPFH有缺失型和非缺失型。非缺失型HPFH的特点是在一个或另一个γ -珠蛋白基因的启动子区域存在点突变，这被认为改变了各种转录因子和启动子之间的相互作用。HPFH的缺失类型被认为解除了γ -珠蛋白基因表达的正常发育模式，因为正常的远端顺式作用因子并置在γ基因附近。这些结局为我们提供了对这些综合征中持续γ基因表达的分子基础的更复杂的理解，并为未来尝试基因治疗β -珠蛋白基因疾病指明了某些策略。
Increased levels of fetal hemoglobin (HbF) can ameliorate the clinical course of inherited disorders of beta-globin gene expression, such as beta thalassemia and sickle cen anemia. In a group of disorders called hereditary persistence of fetal haemoglobin (HPFH), expression of the gamma-globin gene of WP persists at high levels in adult erythroid cells. Molecular studies of the HPFH syndromes have identified several important regulatory elements for the normal pattern of gamma-globin gene expression. Deletion as well as nondeletion types of HPFH have been identified. The nondeletion types of HPFH are characterized by the presence of point mutations, in the promoter region of one or another gamma-globin gene, that are thought to alter interactions between various transcription factors and the promoter. The deletion types of HPFH are thought to deregulate the normal developmental pattern of gamma-globin gene expression due to the juxtaposition of normally distant cis-acting factors into the vicinity of the gamma genes. These Endings have provided us with a more sophisticated understanding of the molecular basis for the persistent gamma-gene expression in these syndromes and point to certain strategies for potential future attempts at gene therapy for beta-globin gene disorders.