Background: 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.
Methods: SNP array analysis in a patient with in a neonate with congenital thrombocytopenia and subsequent aplastic anaemia
Results and conclusions: 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.