Yayınlanmış 1 Ocak 2023 | Sürüm v1
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Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients

Oluşturanlar

  • 1. Karadeniz Tech Univ, Fac Med, Dept Pediat, Div Pediat Allergy & Immunol, Trabzon, Turkiye
  • 2. Natl Inst Allergy & Infect Dis NIAID, Immune Deficiency Genet Sect, Lab Clin Immunol & Microbiol LCIM, NIH, Bethesda, MD USA
  • 3. Erciyes City Hosp, Div Pediat Allergy & Immunol, Kayseri, Turkiye
  • 4. Heinrich Heine Univ, Inst Pharmaceut & Med Chem, Dusseldorf, Germany
  • 5. Shizuoka Childrens Hosp, Dept Allergy & Clin Immunol, Shizuoka, Japan
  • 6. Great Ormond St Hosp Children NHS Fdn Trust, SIHMDS Haematol, London, England
  • 7. UCL, Great Ormond St Inst Child Hlth, Infect Immun & Inflammat Res & Teaching Dept, London, England
  • 8. Karadeniz Tech Univ, Fac Med, Dept Med Genet, Trabzon, Turkiye
  • 9. Great Ormond St Hosp Children NHS Fdn Trust, Dept Immunol & Gene therapy, London, England
  • 10. Gene Engn & Biotechnol Inst, TUBITAK Marmara Res Ctr, Gebze, Turkiye

Açıklama

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 naive 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.

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