The frequency with which mutations occur in some genes that cause immunodeficiency disorders is positively associated with the probability of the occurrence of changes that reverse the genetic defect that causes the disease. This is what researchers at the National Biotechnology Center of the CSIC have observed when analyzing in vitro T lymphocytes of a patient with a primary immunodeficiency.
A detailed analysis of the T lymphocytes of a patient with a rare immunodeficiency has given rise to new clues about an unusual process in which spontaneous mutations that repair the genetic defect that causes the pathology appear.
The work, published in the journal Blood, suggests that the higher the rate of changes that reverse pathological mutations in primary immunodeficiency disorders depends on the intrinsic mutability of these genes.
The patient’s T cells had a defect in a gene that caused a malfunction of his lymphocytes and a severe immunodeficiency. However, the researchers observed that a small population of patient T cells had recovered the expression and function of that gene.
“It was described that in some immunodeficiency disorders, some affected lymphocytes could retrieve the original sequence and thus their function and viability through a process called reversion. However, the reason of this process was not clear. When we analyzed in detail the sequence of the damaged gene in this patient’s T cells, we observed a high sequence variability, which made us wonder if the incidence of reversion could reflect high gene mutability,” explains Hugh Reyburn, lead author of the study.
A computerized analysis, comparing affected genes in primary immunodeficiency disorders where reversion occurred with those where reversion did not occurred, confirmed a high rate of specific variation of the coding region of those who presented reversion.
These data support the hypothesis that the intrinsic mutability of a gene determines the probability of the occurrence of somatic changes capable of reversing the genetic defect that causes the pathology.