A single female patient with a heterozygous variant in LRRC8A was identified with agammaglobulinemia and B cell lymphopenia. T cells were not evaluated in this patient (PMID: 14660746, Sawada A., et al, 2003). However, in a spontaneous mouse model (ebo/ebo), which harbors a homozygous 2 bp frameshift variant in Lrrc8a, which truncates the 15 terminal leucine-rich repeats of the protein, LRCC8A, there is significantly decreased volume-regulated anion channel (VRAC) activity in T cells. These ebo/ebo mice have normal T cell development and function, and intact antibody responses to T-dependent antigens, in contrast to Lrcc8a -/- mice (PMID: 28192143, Platt C., et al, 2017). LRRC8A-formed VRAC appears to be important for T cell activation and function (PMID: 37925509, Wang Y, et al., 2023). Since other patients with B cell deficiency and heterozygous LRRC8A have not been identified, the curation is classified as Limited. p.Ile720ValfsTer?
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