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| Primary immunodeficiency or monogenic inflammatory bowel disease v9.9 | PAX5 |
Boaz Palterer gene: PAX5 was added gene: PAX5 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Mode of inheritance for gene: PAX5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PAX5 were set to 35947077 Phenotypes for gene: PAX5 were set to hypogammaglobulinemia; reduced B cells; sensorimotor deficits; autism spectrum disorder Penetrance for gene: PAX5 were set to unknown Review for gene: PAX5 was set to RED Added comment: Kaiser et al. described 1 patient from 1 kindred, harboring compound heterozygous mutations in the PAX5 gene (p.R31Q / p.E242*). They presented with early-onset recurrent infections, severe hypogammaglobulinemia, a profound reduction of peripheral B cells, severely impaired sensorimotor learning, and autism spectrum disorder (ASD). The underlying mechanism and phenotype were extensively validated using a patient-specific in vivo mutant mouse model (Pax5R31Q/E242* and Pax5R31Q/- mice). These animal models successfully recreated both the immunological and neurological phenotypes, demonstrating an early B-cell developmental block (arrest at the pro-B to pre-B transition), reduced B cell counts in the bone marrow, aberrant cerebellar foliation, and behavioral deficits across ASD domains. Flow cytometry analysis of both the patient's peripheral blood and the murine models confirmed the severe reduction in total B cell numbers and immune arrest. Complete knockout models (Pax5E242*/E242*) demonstrated an absolute failure to generate bone marrow B cells. Sources: Literature |
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