Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
J Med Genet. 2012 Sep;49(9):598-600. doi: 10.1136/jmedgenet-2012-100990.
Gene-targeting studies in mice have revealed a key role for EVI1 protein in the maintenance of haematopoiesis, and argue in favour of a gene dosage requirement for EVI1 in the regulation of haematopoietic stem cells. Furthermore, a fusion transcript of MDS1 and EVI1 has been shown to play a critical role in maintaining long-term haematopoietic stem cell function. Inappropriate activation of EVI1, usually due to a translocation, is a well known and unfavourable change in several myeloid malignancies. It is not known whether haploinsufficiency of any of these genes leads to disease in humans.
SNP array analysis in a patient with in a neonate with congenital thrombocytopenia and subsequent aplastic anaemia
We report for the first time a constitutional deletion encompassing the EVI1 and MDS1 genes in a human, and argue that the deletion causes congenital bone marrow failure in this patient.
小鼠基因靶向研究表明，EVI1 蛋白在维持造血中起着关键作用，并支持 EVI1 在调节造血干细胞方面存在基因剂量要求。此外，MDS1 和 EVI1 的融合转录本已被证明在维持长期造血干细胞功能方面发挥着关键作用。EVI1 的不适当激活，通常由于易位，是几种髓系恶性肿瘤中众所周知的不利变化。目前尚不清楚这些基因中的任何一个杂合缺失是否会导致人类患病。
对一名患有先天性血小板减少症和随后再生障碍性贫血的新生儿进行 SNP 芯片分析
我们首次在人类中报道了一个包含 EVI1 和 MDS1 基因的染色体缺失，并认为该缺失导致了该患者的先天性骨髓衰竭。
