What question did this study set out to answer?

To identify the genetic etiology and pathogenic mechanism linking primary antibody deficiency, sensorimotor deficits, and autism spectrum disorder.

August 10, 2022The Journal of Experimental MedicineOpen Access

Biallelic PAX5 mutations cause hypogammaglobulinemia, sensorimotor deficits, and autism spectrum disorder

View Full Paper

Ask AI

Bookmark

Authors

FKFabian KaiserErasmus MC SGSarah GruenbacherResearch Institute of Molecular Pathology MOMaria Roa OyagaErasmus MC

Discussion

Member takes

Implication

Translational study reveals PAX5 mutations cause hypogammaglobulinemia and autism spectrum disorder in mice and humans, indicating essential roles for PAX5 in midbrain and cerebellar neurogenesis.

Key Points

To identify the genetic etiology and pathogenic mechanism linking primary antibody deficiency, sensorimotor deficits, and autism spectrum disorder.
Identified biallelic mutations in PAX5 in a patient presenting with hypogammaglobulinemia, motor deficits, and autism spectrum disorder.
Engineered patient-specific Pax5 mutant mouse models to evaluate B cell ontogeny, antibody-mediated immunity, neuroanatomy, and autism-related behaviors.
Conducted genetic lineage tracing in mice to determine the physiological role of Pax5 during cerebellar morphogenesis and midbrain neurogenesis.
Pax5 mutant mice exhibited an early block in B cell development leading to defective humoral immune responses and hypogammaglobulinemia, alongside core autism spectrum behavioral deficits.
PAX5 deficiency induced aberrant cerebellar foliation, impaired sensorimotor learning, and profound hypoplasia of the substantia nigra and ventral tegmental area secondary to GABAergic neuron loss.
Mice with heterozygous Pax5 mutations recapitulated the neuroanatomical and behavioral defects observed in homozygous mutants.

Cite This Study

Kaiser et al. (2022) studied this question.

synapsesocial.com/papers/6a8ce2634847f413e42f0558 https://doi.org/10.1084/jem.20220498

View Full Paper

Ask AI

Bookmark

August 10, 2022The Journal of Experimental MedicineOpen Access

Biallelic PAX5 mutations cause hypogammaglobulinemia, sensorimotor deficits, and autism spectrum disorder

View Full Paper

Ask AI

Bookmark

Authors

FKFabian KaiserErasmus MC SGSarah GruenbacherResearch Institute of Molecular Pathology MOMaria Roa OyagaErasmus MC

Discussion

Member takes

Implication

Translational study reveals PAX5 mutations cause hypogammaglobulinemia and autism spectrum disorder in mice and humans, indicating essential roles for PAX5 in midbrain and cerebellar neurogenesis.

Key Points

To identify the genetic etiology and pathogenic mechanism linking primary antibody deficiency, sensorimotor deficits, and autism spectrum disorder.
Identified biallelic mutations in PAX5 in a patient presenting with hypogammaglobulinemia, motor deficits, and autism spectrum disorder.
Engineered patient-specific Pax5 mutant mouse models to evaluate B cell ontogeny, antibody-mediated immunity, neuroanatomy, and autism-related behaviors.
Conducted genetic lineage tracing in mice to determine the physiological role of Pax5 during cerebellar morphogenesis and midbrain neurogenesis.
Pax5 mutant mice exhibited an early block in B cell development leading to defective humoral immune responses and hypogammaglobulinemia, alongside core autism spectrum behavioral deficits.
PAX5 deficiency induced aberrant cerebellar foliation, impaired sensorimotor learning, and profound hypoplasia of the substantia nigra and ventral tegmental area secondary to GABAergic neuron loss.
Mice with heterozygous Pax5 mutations recapitulated the neuroanatomical and behavioral defects observed in homozygous mutants.

Cite This Study

Kaiser et al. (2022) studied this question.

synapsesocial.com/papers/6a8ce2634847f413e42f0558 https://doi.org/10.1084/jem.20220498

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

View Full Paper

Ask AI

Bookmark