Immunodeficiency, Common Variable, 4
A number sign (#) is used with this entry because this form of common variable immunodeficiency, referred to here as CVID4, is caused by homozygous mutation in the BAFFR gene (TNFRSF13C; 606269), which encodes the B-cell activating factor receptor, on chromosome 22q13.
For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
Clinical FeaturesWarnatz et al. (2009) reported a 57-year-old man, born of consanguineous parents, who had a lifelong history of chronic sinusitis and a first episode of pneumonia at age 37 years. At age 57, he received a clinical diagnosis of common variable immunodeficiency syndrome after recurrent pneumonia. His 80-year-old sister had an unremarkable medical history except for a severe Herpes zoster infection at age 70 and recent recurrent pneumonia. Laboratory studies in both individuals showed low levels of serum IgG and IgM, but normal serum and mucosal IgA. Both patients showed a T cell-dependent antigen response to vaccine, but defective T cell-independent humoral responses. Neither patient developed lymphoproliferative or autoimmune disorders. Studies of B lymphocytes from both individuals showed undetectable surface expression of BAFFR and an inability to bind BAFF (TNFSF13B; 603969). Both individuals also had a severe and persistent B-cell lymphopenia and reduced numbers of class-switched memory B cells. Surface protein phenotyping of the B cells showed a developmental arrest after the transitional stage and before the cells became mature follicular B cells.
Molecular GeneticsIn 2 sibs with adult-onset common variable immunodeficiency, Warnatz et al. (2009) identified a homozygous deletion in the BAFFR gene (606269.0001). The authors emphasized the phenotypic differences between the 2 sibs, which suggested a residual sufficient potential to develop B cells that can differentiate and provide host defense even in the absence of BAFFR function.