J Clin Invest. 2012 Jul;122(7):2346-9. doi: 10.1172/JCI63989. Epub 2012 Jun 18.
Mutations in numerous genes encoding ribosomal proteins (RPs) occur in 50%-70% of individuals with Diamond-Blackfan anemia (DBA), establishing the disease as a ribosomopathy. As described in this issue of JCI, Sankaran, Gazda, and colleagues used genome-wide exome sequencing to study DBA patients with no detectable mutations in RP genes. They identified two unrelated pedigrees in which the disease is associated with mutations in GATA1, which encodes an essential hematopoietic transcription factor with no known mechanistic links to ribosomes. These findings ignite an interesting and potentially emotional debate on how we define DBA and whether the term should be restricted to pure ribosomopathies. More generally, the work reflects the powerful knowledge and controversies arising from the deluge of data generated by new genetic technologies that are being used to analyze human diseases.
在 Diamond-Blackfan 贫血（DBA）患者中，有 50%-70%的患者存在编码核糖体蛋白（RP）的众多基因发生突变，这将该疾病确立为一种核糖体病。在本期 JCI 中，Sankaran、Gazda 和同事们利用全基因组外显子组测序，研究了在 RP 基因中未检测到突变的 DBA 患者。他们在两个无关联的家系中发现，该疾病与 GATA1 基因突变有关，GATA1 编码一种必需的造血转录因子，与核糖体没有已知的机制联系。这些发现引发了一场关于如何定义 DBA 以及该术语是否应该仅限于纯核糖体病的有趣且潜在情绪化的争论。更普遍地说，这项工作反映了由新的遗传技术产生的大量数据所带来的强大知识和争议，这些新技术正被用于分析人类疾病。
