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

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. Green open access

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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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