Yakici, Nalan;
Kreins, Alexandra Y;
Catak, Mehmet Cihangir;
Babayeva, Royala;
Erman, Baran;
Kenney, Heather;
Gungor, Hatice Eke;
... Baris, Safa; + view all
(2023)
Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients.
Clinical Immunology
, 255
, Article 109757. 10.1016/j.clim.2023.109757.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.clim.2023.109757 |
| Publisher version: | https://doi.org/10.1016/j.clim.2023.109757 |
| Language: | English |
| Additional information: | Copyright © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | PAX1; Inborn errors of immunity; SCID; thymus; Otofaciocervical syndrome; Hypoparathyroidism |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10177183 |
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