Department of Medical Sciences, and IRCAD Università del Piemonte Orientale A. Avogadro, Alessandria, Novara, Vercelli, Italy.
Hum Mutat. 2010 Dec;31(12):1269-79. doi: 10.1002/humu.21383.
Diamond-Blackfan Anemia (DBA) is characterized by a defect of erythroid progenitors and, clinically, by anemia and malformations. DBA exhibits an autosomal dominant pattern of inheritance with incomplete penetrance. Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients. Experimental evidence supports the hypothesis that DBA is primarily the result of defective ribosome synthesis. By means of a large collaboration among six centers, we report here a mutation update that includes nine genes and 220 distinct mutations, 56 of which are new. The DBA Mutation Database now includes data from 355 patients. Of those where inheritance has been examined, 125 patients carry a de novo mutation and 72 an inherited mutation. Mutagenesis may be ascribed to slippage in 65.5% of indels, whereas CpG dinucleotides are involved in 23% of transitions. Using bioinformatic tools we show that gene conversion mechanism is not common in RP genes mutagenesis, notwithstanding the abundance of RP pseudogenes. Genotype-phenotype analysis reveals that malformations are more frequently associated with mutations in RPL5 and RPL11 than in the other genes. All currently reported DBA mutations together with their functional and clinical data are included in the DBA Mutation Database.
Diamond-Blackfan 贫血症（DBA）的特征是红系祖细胞缺陷，临床上表现为贫血和畸形。DBA 表现出不完全外显的常染色体显性遗传模式。目前已经发现大约 50%的患者存在九个基因（均编码核糖体蛋白 [RP]）的突变。实验证据支持 DBA 主要是核糖体合成缺陷的假说。通过六个中心之间的大型合作，我们在此报告了一项突变更新，其中包括九个基因和 220 个不同的突变，其中 56 个是新的。DBA 突变数据库现在包含了 355 名患者的数据。在已检查遗传的患者中，125 名患者携带新生突变，72 名患者携带遗传突变。移码突变可归因于 65.5%的插入缺失，而 CpG 二核苷酸参与 23%的转换。使用生物信息学工具，我们表明基因转换机制在 RP 基因突变中并不常见，尽管 RP 假基因丰富。基因型-表型分析表明，畸形与 RPL5 和 RPL11 中的突变比其他基因中的突变更频繁相关。所有目前报道的 DBA 突变及其功能和临床数据都包含在 DBA 突变数据库中。
