Agammaglobulinemia 4, mutation in BLK D81.4

This very rare variant of autosomal recessive agammaglobulinemia, also known as AGM4, is caused by a homozygous mutation in the BLNK gene (604515) on chromosome 10q23.2. A corresponding family with this gene defect has been reported previously.

Minegishi et al. identified a homozygous splicing defect in the BLNK gene (604515.0001). The patient's mother and father, who were heterozygous for the mutation, were healthy and had normal concentrations of serum immunoglobulins and normal numbers of B cells. The results suggest that BLNK plays a critical role in orchestrating the transition from pro-B cells to pre-B cells.

The BLK (rs13277113A allele) mutant showed an association with primary Sjögren's syndrome in a larger collective (Montúfar-Robles I et al. 2021). The BLK mutant (rs13277113A/G) was found to be protective for arthritis, and the BANK1 (rs10516487G/A) mutant was protective for both arthritis and keratoconjunctivitis sicca. Montúfar-Robles I et al (2021).

A meta-analysis in Caucasian and Asian populations demonstrated that polymorphisms in the BLK alleles rs13277113 A/G, rs2736340 T/C, and rs2248932 T/C are associated with increased susceptibility to systemic lupus erythematosus SLE (Song GG et al. 2017).

1. Minegishi Yet al. (1999) An essential role for BLNK in human B cell development. Science 286: 1954-1957.
2. Montúfar-Robles I et al. (2021) BLK and BANK1 variants and interactions are associated with susceptibility for primary Sjögren's syndrome and with some clinical features. Cell Immunol 363:104320.
3. Song GG et al. (2017) Association between BLK polymorphisms and susceptibility to SLE: A meta-analysis. Z Rheumatol 76:176-182.