Now in the world there are more than 8 thousand orphan diseases, about 90% of them are hereditary or congenital. Separately, each such disease is extremely rare, and not every doctor generally encounters at least one. However, in sum, the number of patients with rare diagnoses is enormous: only in Russia there are 1.5 million people.
Most orphan diseases are severe pathologies leading to an early death. About 5% of newborns have some kind of genetic anomaly, while about 40% of child deaths occur precisely because of such diseases.
Now the sad list can be replenished with a new diagnosis. So far, the disease has no name and has been identified in only a few patients. The mutation that causes it is located in the BUB1 gene, which is very important for humans. Scientists already know its other defects that lead to the development of cancer. Malfunctioning of this gene is also associated with spontaneous miscarriages.
The BUB1 gene is responsible for cell division in tissues, a process called mitosis. When a cell divides, there is also a division of DNA between the two daughter cells. It is at this moment that mitotic errors can occur, in which DNA is damaged: chromosomes can be destroyed or their number can change. Because of this, mutations in the BUB1 gene are usually considered incompatible with life.
In patients with a new orphan disease, in addition to symptoms visible to the naked eye, such as microcephaly and mental retardation, cells with an abnormal structure and number of chromosomes were also found. And although the molecular mechanisms underlying these errors were different in patients, they were associated with the BUB1 gene.
Scientists note that the new disease provides a lot of information about how BUB1 is involved in brain formation. Research results show that in the early stages, our brain is very sensitive to mitotic errors. Presumably due to improper division, cell death occurs, it is because of this that microcephaly has become a characteristic symptom.
“In children with primary microcephaly and multiple congenital malformations, germline mutations in BUB1 should be considered as the cause more often than has been done so far,” says Ingrid Bader, MD and co-author of the study.