In humans, loss-of-function mutations in DIAPH1 are associated with immunodeficiency, microcephaly, and mitochondrial dysfunction (29, 30); whereas mutations in DAD, resulting from deletion or modification of the RRKR motif (22, 31), for example, in the DIAPH1-(R1213X) where the RRKR motif is deleted, confer gain-of-function that have been implicated in autosomal dominant hearing loss (24) and macrothrombocytopenia (32). This evidence concerns the gene DIAPH1 and immunodeficiency disease.