Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism.
Diamond Blackfan Anemia at the Crossroad between Ribosome Biogenesis and Heme Metabolism.
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DOI：
10.1155/2010/790632
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发表时间：
2010
影响因子：
--
通讯作者：
Tolosano E
中科院分区：
文献类型：
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作者：
Chiabrando D;Tolosano E
Diamond-Blackfan贫血（DBA）是一种罕见的纯红细胞发育不全，出现在婴儿期。大约40%的病例与其他先天性缺陷有关，特别是上肢或颅面区域的畸形。编码核糖体蛋白RPS 19的基因突变已在25%的DBA患者中被鉴定，导致18 S rRNA加工和40 S核糖体亚基形成受损。此外，其他核糖体蛋白编码基因的突变约占其他DBA病例的25%。最近，对编码血红素输出体猫白血病病毒C亚群受体（FLVCR 1）的基因缺失的小鼠的分析表明，该基因可能参与DBA的发病机制。FLVCR 1基因敲除小鼠表现出与DBA患者相似的表型，包括红细胞衰竭和畸形。有趣的是，一些DBA患者与染色体1 q31有疾病联系，FLVCR 1位于染色体1 q31上。此外，据报道，来自DBA患者的细胞表达编码非功能性蛋白的FLVCR 1的选择性剪接同种型。在此，我们回顾了已知的作用RPS 19和FLVCR 1在核糖体功能和血红素代谢分别，并讨论如何缺乏核糖体蛋白或血红素出口商可能会导致相同的表型。
Diamond-Blackfan anemia (DBA) is a rare, pure red-cell aplasia that presents during infancy. Approximately 40% of cases are associated with other congenital defects, particularly malformations of the upper limb or craniofacial region. Mutations in the gene coding for the ribosomal protein RPS19 have been identified in 25% of patients with DBA, with resulting impairment of 18S rRNA processing and 40S ribosomal subunit formation. Moreover, mutations in other ribosomal protein coding genes account for about 25% of other DBA cases. Recently, the analysis of mice from which the gene coding for the heme exporter Feline Leukemia Virus subgroup C Receptor (FLVCR1) is deleted suggested that this gene may be involved in the pathogenesis of DBA. FLVCR1-null mice show a phenotype resembling that of DBA patients, including erythroid failure and malformations. Interestingly, some DBA patients have disease linkage to chromosome 1q31, where FLVCR1 is mapped. Moreover, it has been reported that cells from DBA patients express alternatively spliced isoforms of FLVCR1 which encode non-functional proteins. Herein, we review the known roles of RPS19 and FLVCR1 in ribosome function and heme metabolism respectively, and discuss how the deficiency of a ribosomal protein or of a heme exporter may result in the same phenotype.