Functional analysis of a new genetic variant suspected to cause a novel form of primary immunodeficiency featuring frequent respiratory infections, a susceptibility to herpesviral infection and lymphoid malignancy in three individuals.

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The main goal of this project is to test the hypothesis that inherited mutations in a particular gene can cause a novel form of primary immunodeficiency. DNA sequencing was carried out to discover the genetic change underlying a familial immunodeficiency that featured frequent respiratory infections, a susceptibility to herpesviral infection and lymphoid malignancy. The three affected individuals, in two generations of one family, share a novel genetic change affecting the amino acid sequence of a signaling adaptor protein. This protein is known to be important for specialized functions of immune cells including their ability to move towards sites of inflammation and to kill infected target cells.  However, there are no examples of human disease connected to this protein to date. We plan to study lymphoid cells of the patients functionally to unravel a suspected underlying inborn error of immunity and characterise it in molecular terms. This may suggest ways to diagnose and treat other patients with the same disorder.