Analysis of the recovery of CD247 expression in a PID patient: Insights into the spontaneous repair of defective genes

Alfonso Blázquez-Moreno, Adriana Pérez-Portilla, Miriam Agúndez-llaca, Daniela Dukovska, Mar Valés-Gómez, Cigdem Aydogmus, Aydan Ikinciogullari, José R. Regueiro and Hugh T. Reyburn

Key points

  • The propensity of genes to mutate influences the probability of spontaneous reversion of genetic defects in primary immunodeficiency.


Mutations in T-cell antigen receptor (TCR) subunits genes cause rare immunodeficiency diseases characterized by impaired expression of the TCR at the cell surface and selective T lymphopenia. Here detailed analyses of spontaneously arising somatic mutations that recover CD247, and so TCR expression, in a newly identified CD247 deficient patient are described. The recovery of CD247 expression in some patient T cells was associated with both reversion of the inactivating mutation and a variant with a compensating mutation that could reconstitute TCR expression, but not as efficiently as wild-type CD247. Multiple mutations were found in CD247 cDNAs cloned from the patient as well as in cDNA and genomic DNA from other individuals suggesting that genetic variation in this gene is frequent. Analyses of other genes mutated in primary immunodeficiencies where reversions have been described also revealed a higher rate of mutation than that observed for genes mutated in immunodeficiency where revertants have not been identified or control genes. These data support the hypothesis that the occurrence of somatic mutations that may reconstitute genetic defects in primary immunodeficiency is related to an increased propensity of those genes to mutate.

  • Submitted January 17, 2017.
  • Accepted July 18, 2017.