To find such a mutation the Tomsk geneticists conducted a study involving more than 300 women with a pregnancy loss.
Elizaveta Fonova
"We wondered if the presence of the hidden mutation on the X chromosome of healthy women might cause a miscarriage. Usually women have random inactivation of the X chromosome: half of the cells have active X chromosome received from the mother, and the other half — from the father. But in some cases there is a displacement when, for instance, the X chromosome inherited from one of the parents ‘shuts down’ in 90% of cells or even more. In such cases woman may be the carrier of the X-chromosome mutation and not even know about it because her mutated X chromosome ‘does not work’, ” says Elizaveta Fonova, the junior researcher of the developmental biology laboratory at the Research Institute of Medical Genetics of Tomsk NRMC.
According to the scientist, one-third of female patients that were diagnosed with a significant aberration from the equiprobable X chromosome inactivation did have microstructural chromosomal abnormalities on it indeed. They had not manifest themselves in these women but caused the miscarriage and fetal death.
Igor Lebedev
“Analysis of the nature of X chromosome inactivation can be used as an additional test for women who have faced the problem of miscarriage or have a baby with inherited disease caused by mutations in gene on the X chromosome. In such cases a woman may be the carrier of pathogenic variant that doesn’t affect her health due to the random inactivation or silencing of such X chromosome. However, when transmitting a mutation to offspring, the variant may manifest itself as a hereditary disease, especially in sons since they have only one X chromosome of maternal origin. It can also lead to a miscarriage,” says Igor Lebedev, the Deputy Director for Research of Tomsk NRMC, the RAS professor, the head of the developmental biology laboratory at the RIMG of Tomsk NRMC and the Doctor of Biological Sciences.
In such cases, while planning the next pregnancy, a woman must be suggested the prenatal diagnostic test. If there are mutations affecting the fetal viability, it is advisable to consider applying the method of in vitro fertilization (IVF) and the preimplantation genetic testing. This approach will ensure the transfer of the embryo without hereditary mutations on the X chromosome and wait for a healthy pregnancy.
● You can get tested for such a mutation at the Research Institute of Medical Genetics of Tomsk NRMC. Research results were published in Cytogenetic and Genome Research scientific journal. The research was supported by Russian Science Foundation (№ 21-65-00017)