Journal Article

FZJ-2023-03513

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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. ; 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. ; Bulutoglu, A. ; Eltan, S. B. ; Altunbas, M. Y. ; Bayram, F. ; Karakus, I. S. ; Karatay, E. ; Tekeoglu, S. D. ; Eser, M. ; Albayrak, D. ; Citli, S. ; Kiykim, A. ; Karakoc-Aydiner, E. ; Ozen, A. ; Ghosh, S. ; Gohlke, H.FZJ* ; Orhan, F. ; Notarangelo, L. D. ; Davies, E. G. ; Baris, S. (Corresponding author)

2023
Academic Press Orlando, Fla.

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Please use a persistent id in citations: doi:10.1016/j.clim.2023.109757  doi:10.34734/FZJ-2023-03513

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.

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Contributing Institute(s):

1. Bioinformatik (IBG-4)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. 2171 - Biological and environmental resources for sustainable use (POF4-217) (POF4-217)
3. GRK 2158 - GRK 2158: Naturstoffe und Analoga gegen Therapie-resistente Tumoren und Mikroorganismen: Neue Leitstrukturen und Wirkmechanismen (270650915) (270650915)

Appears in the scientific report 2023

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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