Journal of Clinical Immunology

, Volume 39, Issue 2, pp 144–147 | Cite as

A Novel FOXN1 Variant Is Identified in Two Siblings with Nude Severe Combined Immunodeficiency

  • Sinem Firtina
  • Funda Cipe
  • Yuk Yin Ng
  • Ayca Kiykim
  • Ozden Hatirnaz Ng
  • Tugce Sudutan
  • Cigdem Aydogmus
  • Safa Baris
  • Gulyuz Ozturk
  • Elif Aydiner
  • Ahmet Ozen
  • Muge SayitogluEmail author
Letter to Editor

To the Editor,

Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiencies (PIDs) caused by gene variants that lead to a failure of functional T cell development, with or without accompanying defects in the production of B and/or NK cells [1]. Deleterious variants in more than 20 genes have been implicated in SCID [2]. The FOXN1 (Forkhead Box N1) deficiency, also known as the nude SCID, is a very rare autosomal recessive form of SCIDs. It has a unique phenotype with severe T cell immunodeficiency with normal B and NK cells, thymus dysgenesis, congenital alopecia, and nail dystrophy [3]. Due to the pleiotropic effects of FOXN1, the patients present with non-immunological features in addition to the classical TB+NK+ SCID, with mainly the skin and hair being affected including abnormal hair keratinization and absence of hair [4].

FOXN1gene (located in 17q11.2) encodes a transcription factor that regulates the development, differentiation, and function...



We would like to thank to Monica Ann Ozkan, MSN, RN, and CPAN (Bezmialem Vakif University) in language editing for this paper and Dr. Luisa Imberti from Laboratorio CREA, AO Spedali Civili di Brescia for providing the TREC-KREC-TRAC plasmid.

Funding Information

This project is supported by Istanbul University Research Fund (No: 52575 and 20499) and Istanbul Bilgi University [Y.Y Ng, 2017)].

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

Supplementary material

10875_2019_615_MOESM1_ESM.docx (9.6 mb)
ESM 1 (DOCX 9848 kb)


  1. 1.
    Fischer A, et al. Severe combined immunodeficiencies and related disorders. Nat Rev Dis Primers. 2015;1:15061.CrossRefGoogle Scholar
  2. 2.
    Picard C, al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35(8):696–726.CrossRefGoogle Scholar
  3. 3.
    Gallo V, Cirillo E, Giardino G, Pignata C. FOXN1 deficiency: from the discovery to novel therapeutic approaches. J Clin Immunol. 2017;37:751–8.CrossRefGoogle Scholar
  4. 4.
    Flanagan SP. ‘Nude’, a new hairless gene with pleiotropic effects in the mouse. Genet Res. 1966;8(3):295–309.CrossRefGoogle Scholar
  5. 5.
    Nehls M, Pfeifer D, Schorpp M, Hedrich H, Boehm T. New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature. 1994;372(6501):103–7.CrossRefGoogle Scholar
  6. 6.
    Amorosi S, D’Armiento M, Calcagno G, Russo I, Adriani M, Christiano AM, et al. FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic nude/SCID fetus. Clin Genet. 2008;73(4):380–4.CrossRefGoogle Scholar
  7. 7.
    Vigliano I, Gorrese M, Fusco A, Vitiello L, Amorosi S, Panico L, et al. FOXN1 mutation abrogates prenatal T-cell development in humans. J Med Genet. 2011;48(6):413–6.CrossRefGoogle Scholar
  8. 8.
    Adriani M, Martinez-Mir A, Fusco F, Busiello R, Frank J, Telese S, et al. Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population. Ann Hum Genet. 2004;68(Pt 3):265–8.CrossRefGoogle Scholar
  9. 9.
    Markert ML, Marques JG, Neven B, Devlin BH, McCarthy EA, Chinn IK, et al. First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood. 2011;117(2):688–96.CrossRefGoogle Scholar
  10. 10.
    Chou J, Massaad MJ, Wakim RH, Bainter W, Dbaibo G, Geha RS. A novel mutation in FOXN1 resulting in SCID: a case report and literature review. Clin Immunol. 2014;155(1):30–2.CrossRefGoogle Scholar
  11. 11.
    Firtina S, Ng YY, Ng OH, Nepesov S, Yesilbas O, Kilercik M, et al. A novel pathogenic frameshift variant of CD3E gene in two T-B+ NK+ SCID patients from Turkey. Immunogenetics. 2017;69:653–9.CrossRefGoogle Scholar
  12. 12.
    Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4(7):1073–81.CrossRefGoogle Scholar
  13. 13.
    Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248–9.CrossRefGoogle Scholar
  14. 14.
    Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods. 2014;11(4):361–2.CrossRefGoogle Scholar
  15. 15.
    Morinishi Y, Imai K, Nakagawa N, Sato H, Horiuchi K, Ohtsuka Y, et al. Identification of severe combined immunodeficiency by T-cell receptor excision circles quantification using neonatal Guthrie cards. J Pediatr. 2009;155(6):829–33.CrossRefGoogle Scholar
  16. 16.
    Nakagawa N, Imai K, Kanegane H, Sato H, Yamada M, Kondoh K, et al. Quantification of kappa-deleting recombination excision circles in Guthrie cards for the identification of early B-cell maturation defects. J Allergy Clin Immunol. 2011;128(1):223–225 e2.CrossRefGoogle Scholar
  17. 17.
    Pignata C, Fiore M, Guzzetta V, Castaldo A, Sebastio G, Porta F, et al. Congenital alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs. Am J Med Genet. 1996;65(2):167–70.CrossRefGoogle Scholar
  18. 18.
    Frank J, Pignata C, Panteleyev AA, Prowse DM, Baden H, Weiner L, et al. Exposing the human nude phenotype. Nature. 1999;398(6727):473–4.CrossRefGoogle Scholar
  19. 19.
    Radha Rama Devi A, Panday NN, Naushad SM. FOXN1 Italian founder mutation in Indian family: implications in prenatal diagnosis. Gene. 2017;627:222–5.CrossRefGoogle Scholar
  20. 20.
    Su DM, Navarre S, Oh WJ, Condie BG, Manley NR. A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation. Nat Immunol. 2003;4(11):1128–35.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sinem Firtina
    • 1
    • 2
  • Funda Cipe
    • 3
  • Yuk Yin Ng
    • 4
  • Ayca Kiykim
    • 5
  • Ozden Hatirnaz Ng
    • 1
    • 6
  • Tugce Sudutan
    • 1
  • Cigdem Aydogmus
    • 3
  • Safa Baris
    • 7
  • Gulyuz Ozturk
    • 8
  • Elif Aydiner
    • 7
  • Ahmet Ozen
    • 7
  • Muge Sayitoglu
    • 1
    Email author
  1. 1.Department of Genetics, Aziz Sancar Institute of Experimental MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Department of Molecular Biology and GeneticsIstinye UniversityIstanbulTurkey
  3. 3.Department of Pediatric Allergy and InfectionIstanbul Kanuni Sultan Suleyman Training and Research HospitalIstanbulTurkey
  4. 4.Department of Genetics and BioengineeringIstanbul Bilgi UniversityIstanbulTurkey
  5. 5.Department of Pediatric Allergy and InfectionIstanbul University Cerrahpasa Medical FacultyIstanbulTurkey
  6. 6.Department of Medical BiologyAcibadem Mehmet Ali Aydinlar University Medical Faculty IstanbulIstanbulTurkey
  7. 7.Department of Pediatric Allergy and ImmunologyMarmara UniversityIstanbulTurkey
  8. 8.Pediatric Bone Marrow Transplantation UnitAcibadem Atakent HospitalIstanbulTurkey

Personalised recommendations