Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients
Citation
Yakici, N., Kreins, A. Y., Catak, M. C., Babayeva, R., Erman, B., Kenney, H., Gungor, H. E., Cea, P. A., Kawai, T., Bosticardo, M., Delmonte, O. M., Adams, S., Fan, Y. T., Pala, F., Turkyilmaz, A., Howley, E., Worth, A., Kot, H., Sefer, A. P., Kara, A., … Baris, S. (2023). Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients. Clinical immunology (Orlando, Fla.), 255, 109757. https://doi.org/10.1016/j.clim.2023.109757Abstract
Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical
syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance.
Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic
aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6
patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T
cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo
differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic
cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism
(n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our
results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment.
