Submission Details

CD79A was first reported in relation to autosomal recessive agammaglobulinemia 3 in 1999 (Minegishi Y, et al., 1999; PMID: 10525050). CD79A encodes Igα, which is part of the B-cell antigen receptor (BCR) complex and is required, in cooperation with Igβ, for initiation of the signal transduction cascade. Agammaglobulinemia 3 is a primary immunodeficiency characterized by profoundly low or absent serum immunoglobulins and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals are susceptible to recurrent infections. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. The mechanism of disease is homozygous loss of function and seven unique variants have been reported in humans, including nonsense, frameshift, and splicing. Variants in this gene have been reported in at least 7 probands in 6 publications (PMIDs: 11920841, 10525050, 29335801, 24481606, 19302039, 31696364), and segregated with disease in one additional family member (PMID: 31696364). Experimentally, this gene-disease relationship is supported by its expression in B cells (PMID: 1729378), its role in BCR signal transduction (PMID: 7688784), which is altered in patient cells (PMID: 10525050), and its interaction with BLNK in the signaling pathway (PMID: 11909947). Further support is provided by at least two mouse models (PMIDs: 8650582, 12097390), which recapitulate features of agammaglobulinemia. In summary CD79A is definitively associated with autosomal recessive agammaglobulinemia 3. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.