Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients

YAKICI N., Kreins A. Y., Catak M. C., Babayeva R., ERMAN B., Kenney H., ...More

Clinical immunology (Orlando, Fla.), vol.255, pp.109757, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 255
  • Publication Date: 2023
  • Doi Number: 10.1016/j.clim.2023.109757
  • Journal Name: Clinical immunology (Orlando, Fla.)
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.109757
  • Keywords: Hypoparathyroidism, Inborn errors of immunity, Otofaciocervical syndrome, PAX1, SCID, thymus
  • Recep Tayyip Erdoğan University Affiliated: Yes


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.