TY  - JOUR
AU  - Graafen, Lea
AU  - Borkhardt, Arndt
AU  - Reiß, Julian
AU  - Soura, Stavrieta
AU  - Laws, Hans-Jürgen
AU  - Uhrberg, Markus
AU  - Paulusch, Stefan
AU  - De Domenico, Elena
AU  - Beyer, Marc D
AU  - Bennstein, Sabrina B
AU  - Ghosh, Sujal
TI  - FOXN1 immunodeficiency detected by TREC-based newborn screening - A challenge of management?
JO  - Immunology letters
VL  - 279
SN  - 0165-2478
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2026-00268
SP  - 107142
PY  - 2026
AB  - 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.
KW  - Humans
KW  - Infant, Newborn
KW  - Disease Management
KW  - Forkhead Transcription Factors: genetics
KW  - Forkhead Transcription Factors: deficiency
KW  - Genetic Association Studies
KW  - Immunologic Deficiency Syndromes: diagnosis
KW  - Immunologic Deficiency Syndromes: genetics
KW  - Immunophenotyping
KW  - Mutation
KW  - Neonatal Screening: methods
KW  - Severe Combined Immunodeficiency: diagnosis
KW  - Severe Combined Immunodeficiency: genetics
KW  - T-Lymphocytes: immunology
KW  - FOXN1 (Other)
KW  - Nude SCID (Other)
KW  - SCID (Other)
KW  - TREC-NBS (Other)
KW  - Thymic deficiency (Other)
KW  - scRNA-seq (Other)
KW  - Forkhead Transcription Factors (NLM Chemicals)
KW  - Whn protein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41610918
DO  - DOI:10.1016/j.imlet.2026.107142
UR  - https://pub.dzne.de/record/285629
ER  -