The research group led by Associate Professor Tetsuya Shinbori of the Graduate School of Medicine, Tohoku University is a congenital bone disease that combines radioulnar synostosis and amegakaryocyte thrombocytopenia. I found a new causative gene.
Radioulnar synostosis with amegakaryocyte thrombocytopenia is a disease in which blood cells are reduced and two bones in the forearm are fused.So far, there have been only about 2 families, and mutations in the causative gene HOXA10 have been reported in 2 of them, but in some cases no mutations have been confirmed in this gene, suggesting the existence of another causative gene. rice field.
Therefore, in this study, we performed genetic analysis of patients with no confirmed mutation in HOXA11 and their healthy parents, and searched for genetic changes that were not seen in the parents and occurred only in the patients themselves.As a result, we confirmed a missense mutation in EVI1, which is a protooncogene that is highly expressed in leukemia, colorectal cancer, ovarian cancer, etc. (one of the amino acids that make up the protein is replaced by another amino acid). ..In addition, genetic analysis of two patients with the same disease revealed that the mutations were concentrated in a specific region of EVI2, which plays an important role not only in blood cell proliferation but also in forearm development. Was suggested.
Although it was already known that EVI1 is highly expressed in cancer, this study revealed for the first time that a congenital missense mutation in EVI1 causes a decrease in blood cells.This discovery is expected to advance the development of treatments for cancers with high EVI1 expression in the future.
