Table 2.

Overview of patients with a heterozygous FOXN1 variant identified from TREC-based NBS

IDVariantaReferralT cells, per µl blood (% naive)bRadiological assessment of thymusNail dystrophy and/or skin manifestationsInfectionsProphylactic treatmentOther comorbidityFollow-up timecFollow-up ongoing
FOX-1 c.831-2A > G
p.?
Likely pathogenic 
Non-urgent (pilot) CD3+: 900
CD4+: 630 (41.3%)
CD8+: 260 (92.3%) 
ND No Viral infections, recurrent acute otitis media Antiviral (for 3.5 mo, started 8.5 mo after referral) No >5 years Yes 
FOX-2 c.311T > C
p.(Phe104Ser)
VUS 
Urgent CD3+: 1,080
CD4+: 820 (62.8%)
CD8+: 250 (100%) 
ND No No No JMML 1 mo No 
FOX-3 c.143del p.(Cys48fs)
Pathogenic 
Non-urgent CD3+: 1,140
CD4+: 770 (ND)
CD8+: 310 (ND) 
ND No No No No >2 years No 
FOX-4 c.1079T > C
p.(Leu360Pro)
VUS 
Urgent CD3+: 1,320
CD4+: 1,040 (77.3%)
CD8+: 300 (88.7%)
RTE: 64% 
ND Eczema No No Gastro-intestinal complaints >1 year No 
FOX-5 c.1267del
p.(Leu423Cysfs*127)
Likely pathogenic 
Urgent CD3+: 472
CD4+: 444 (61.9%)
CD8+: 27 (72%) 
Small (X-thorax) No No Antibacterial (for 6 mo after referral), IGRT (for 5 mo, started 1 mo after referral) No >1.25 years Yes 
FOX-6 c.143del p.(Cys48fs)
Pathogenic 
Urgent CD3+: 1,050
CD4+: 840 (73.8%)
CD8+: 210 (95.2%) 
ND No No No No >4 mo Yes 
IDVariantaReferralT cells, per µl blood (% naive)bRadiological assessment of thymusNail dystrophy and/or skin manifestationsInfectionsProphylactic treatmentOther comorbidityFollow-up timecFollow-up ongoing
FOX-1 c.831-2A > G
p.?
Likely pathogenic 
Non-urgent (pilot) CD3+: 900
CD4+: 630 (41.3%)
CD8+: 260 (92.3%) 
ND No Viral infections, recurrent acute otitis media Antiviral (for 3.5 mo, started 8.5 mo after referral) No >5 years Yes 
FOX-2 c.311T > C
p.(Phe104Ser)
VUS 
Urgent CD3+: 1,080
CD4+: 820 (62.8%)
CD8+: 250 (100%) 
ND No No No JMML 1 mo No 
FOX-3 c.143del p.(Cys48fs)
Pathogenic 
Non-urgent CD3+: 1,140
CD4+: 770 (ND)
CD8+: 310 (ND) 
ND No No No No >2 years No 
FOX-4 c.1079T > C
p.(Leu360Pro)
VUS 
Urgent CD3+: 1,320
CD4+: 1,040 (77.3%)
CD8+: 300 (88.7%)
RTE: 64% 
ND Eczema No No Gastro-intestinal complaints >1 year No 
FOX-5 c.1267del
p.(Leu423Cysfs*127)
Likely pathogenic 
Urgent CD3+: 472
CD4+: 444 (61.9%)
CD8+: 27 (72%) 
Small (X-thorax) No No Antibacterial (for 6 mo after referral), IGRT (for 5 mo, started 1 mo after referral) No >1.25 years Yes 
FOX-6 c.143del p.(Cys48fs)
Pathogenic 
Urgent CD3+: 1,050
CD4+: 840 (73.8%)
CD8+: 210 (95.2%) 
ND No No No No >4 mo Yes 

IGRT, immunoglobulin replacement therapy; ND, not determined; RTE, recent thymic emigrant; VUS, variant of uncertain significance.

a

Transcript: NM_001369369.1.

b

First immunophenotyping results after referral from NBS.

c

Refers to immunological follow-up specifically.

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