Mutation-dependent selective effects during early embryonic development in hereditary angioedema

Published: December 06, 2021

Hereditary angioedema (HAE) may be due to a genetic deficiency of functional C1 inhibitor (C1-INH) or linked with mutations in various other genes but with normal C1-INH level and function (HAEnCI). Although the types of HAE-C1-INH and HAEnCI are autosomally dominant inherited there is an impression that in HAEnCI more females carry disease-linked mutations. The study of Bork et al. in The Journal of Allergy and Clinical Immunology: In Practice analyzed HAE-specific mutations passed on to the next generations in a high number of families with various types of HAE.

The results showed that in all HAE types, less male and more female offspring of mutation carriers than expected for autosomal dominant inheritance inherited the familial mutation. In addition, there were less male offspring than expected in HAEnCI. This was independent of paternal or maternal inheritance. Patients did not report an increased number of miscarriages. In conclusion, there is a sex- and mutation-dependent selection during early embryogenesis, possible around the time of implantation, favoring male wild-type and female mutant embryos. It also appears that in HAEnCI, 20 – 25% of male embryos carrying the HAE mutation are lost. These findings point out that there is a potentially important role of the kallikrein-kinin system during early embryonic development.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

Full Article