Name: Immunodeficiency, common variable, 20 | Acronym: CVID20
Alt. names: Autosomal dominant BLK loss-of-function / haploinsufficiency

Gene: BLK | MOI: Autosomal dominant | Mechanism of action: Haploinsufficiency

No. of cases in DB: 2 | First reported in: 2015

Last updated on: 2024-01-14 09:53:46 by Xiao P. Peng

OMIM:

Orphanet: -

MONDO: -

DOID: -

ClinGen:

Compeer et al. (2015) identified a heterozygous missense BLK variant in 2 related patients with CVID diagnoses (PMID: 25926555). The index patient presented at age 7 with a history of severe recurrent pulmonary infections since age 8 months old with hypogammaglobulinemia (particularly low IgG and IgA) and suboptimal vaccine responses on labs. Her father who shared her variant had a history of recurrent respiratory tract infections and episodes of bacteriemia from small skin lesions, along with relatively low IgM and IgG levels. Neither had signs for autoimmunity or lymphoproliferative disease. The index patient's mother, sister and another brother showed no clinical symptoms related to antibody deficiency and did not share the BLK variant. The authors showed that the family's L3P-BLK variant led to distorted BCR signaling resulting in abnormal B-cell proliferation and recruitment of antigen-specific CD4+ T-cell help, consistent with the patients' reduced numbers of total CD19+ B cells and class-switched memory B-cells and defective production of high affinity antibodies.

Patients were managed on intravenous immunoglobulin supplementation (IVIG) and antibiotic prophylaxis (PMID: 25926555).