CTLA4 and immune system disorder: ,117 Given the variable expressivity, which is relatively common among disorders of immune dysregulation, such as the CTLA-4 insufficiency and the STAT3 gain-of-function,13,14 on several occasions, segregation analysis has revealed typical rheumatic disease without significant evidence of immunodeficiency to segregate with a deleterious mutation in families, where the index patient came to attention and was subjected to genetic sequencing due to their immunodeficiency.118