Abstract
Defects causing severe combined immunodeficiency (SCID) have been reported in pathways mediating antigen receptor rearrangement, antigen receptor and cytokine signaling, and purine metabolism. Recognizing that the actin regulator Coronin-1A is essential for development of a normal peripheral T cell compartment in mouse models, we identified absence of Coronin-1A in a girl with T-B+NK+ SCID who suffered recurrent infections including severe post-vaccination varicella at age 13 months. Murine Coronin-1A is essential for the release of T cells from the thymus, consistent with the paradoxically detectable thymus in our patient. Molecular analysis revealed a 2 bp deletion in the paternal CORO1A coding sequence paired with a 600 kb de novo deletion encompassing CORO1A on the maternal allele. This genomic region at 16p11.2 is subject to recurrent copy number variations associated with autism spectrum disorders, including attention deficit and hyperactivity, present in our patient. This case highlights the first link between actin cytoskeleton regulation and SCID.