Journal Article

DZNE-2026-00268

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png FOXN1 immunodeficiency detected by TREC-based newborn screening - A challenge of management?

Graafen, L. ; Borkhardt, A. ; Reiß, J. ; Soura, S. ; Laws, H.-J. ; Uhrberg, M. ; Paulusch, S.DZNE* ; De Domenico, E.DZNE* ; Beyer, M. D.DZNE* ; Bennstein, S. B. ; Ghosh, S.

2026
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.imlet.2026.107142

Abstract: Incomplete genotype-phenotype correlations challenge the management of non-SCID FOXN1 immunodeficiency. We describe the detailed clinical course of three distinct newborns with four novel FOXN1 mutations identified by TRECNBS. For comprehensive immune characterization advanced flow cytometry-based immunophenotyping was employed alongside high-resolution single-cell RNA sequencing. In our cohort, we detected heterozygous FOXN1 mutations in P1 (c.1178delG; p.Gly393Alafs*157) and P2 (c.830+1G>T; p.?), and compound heterozygous FOXN1-mutations in P3 (c.1318C>T; p.Gln440* and c.668T>G; p.?). Despite slow and partial recovery from T-cell lymphocytopenia in P3, clinical signs for classical 'nude SCID` were incomplete. Compared to a healthy cord blood control, a distinct B-cell population was identified in the FOXN1-deficient patients expressing immature B-cell markers and lower HLA-II mRNA levels. In summary, our cohort of three newborns with four novel FOXN1 variants highlights heterogeneous immunological courses and broader thymic dysfunction implications in this rare disease. Structured management strategies are essential for those identified by NBS-programs.

Keyword(s): Humans (MeSH) ; Infant, Newborn (MeSH) ; Disease Management (MeSH) ; Forkhead Transcription Factors: genetics (MeSH) ; Forkhead Transcription Factors: deficiency (MeSH) ; Genetic Association Studies (MeSH) ; Immunologic Deficiency Syndromes: diagnosis (MeSH) ; Immunologic Deficiency Syndromes: genetics (MeSH) ; Immunophenotyping (MeSH) ; Mutation (MeSH) ; Neonatal Screening: methods (MeSH) ; Severe Combined Immunodeficiency: diagnosis (MeSH) ; Severe Combined Immunodeficiency: genetics (MeSH) ; T-Lymphocytes: immunology (MeSH) ; FOXN1 ; Nude SCID ; SCID ; TREC-NBS ; Thymic deficiency ; scRNA-seq ; Forkhead Transcription Factors ; Whn protein

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Contributing Institute(s):

1. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)
2. Immunogenomics and Neurodegeneration (AG Beyer)
3. Platform for Single Cell Genomics and Epigenomics (PRECISE)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
2. 351 - Brain Function (POF4-351) (POF4-351)
3. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; 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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