A Novel Missense LIG4 Mutation in a Patient With a Phenotype Mimicking Behçet’s Disease

  • Ekim Z. Taskiran
  • Hafize E. Sonmez
  • Can Kosukcu
  • Ece Tavukcuoglu
  • Gozde Yazici
  • Gunes Esendagli
  • Ezgi D. Batu
  • Pelin O. S. Kiper
  • Yelda Bilginer
  • Mehmet Alikasifoglu
  • Seza OzenEmail author
Original Article


DNA ligase IV (LIG4) syndrome is a rare autosomal recessive disorder, manifesting with variable immune deficiency, growth failure, predisposition to malignancy, and cellular sensitivity to ionizing radiation. The facial features are subtle and variable, as well. Herein, we described an 18-year-old boy, the first child of consanguineous parents who presented with Behçet’s disease (BD)-like phenotype, developmental delay, and dysembryoplastic neuroepithelial tumor (DNET). Whole-exome sequencing revealed a homozygous p.Arg871His (c.2612G > A) mutation in LIG4. To date, 35 cases have been reported with LIG4 syndrome. Peripheral blood mononuclear cells of the patient displayed notable sensitivity to ionizing radiation. Flow cytometric annexin V-propidium iodide (PI) and eFluor670 proliferation assays showed accelerated radiation-induced apoptosis and diminished proliferation, respectively. To our knowledge, this is the first case presenting with a BD-like phenotype. This case provides further evidence that rare monogenic defects could be the underlying cause of atypical presentations of some well-described disorders. Moreover, this clinical report further expands the phenotypical spectrum of LIG4 deficiency.


DNA ligase IV LIG4 syndrome Behçet’s disease whole exome sequencing 



We acknowledge the INSAID project (E-rare 2015, 15-pp-156) and Tubitak project (315S096).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

10875_2018_587_MOESM1_ESM.docx (27 kb)
ESM 1 (DOCX 26 kb)


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Copyright information

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

Authors and Affiliations

  • Ekim Z. Taskiran
    • 1
  • Hafize E. Sonmez
    • 2
  • Can Kosukcu
    • 3
  • Ece Tavukcuoglu
    • 4
  • Gozde Yazici
    • 5
  • Gunes Esendagli
    • 4
  • Ezgi D. Batu
    • 2
  • Pelin O. S. Kiper
    • 6
  • Yelda Bilginer
    • 2
  • Mehmet Alikasifoglu
    • 1
  • Seza Ozen
    • 2
    Email author
  1. 1.Department of Medical GeneticsHacettepe University Faculty of MedicineAnkaraTurkey
  2. 2.Department of Pediatrics, Division of RheumatologyHacettepe University Faculty of MedicineAnkaraTurkey
  3. 3.Department of Bioinformatics, Institute of Health SciencesHacettepe UniversityAnkaraTurkey
  4. 4.Department of Basic OncologyHacettepe University Cancer InstituteAnkaraTurkey
  5. 5.Faculty of Medicine, Department of Radiation OncologyHacettepe UniversityAnkaraTurkey
  6. 6.Department of Pediatrics, Division of Pediatric GeneticsHacettepe University Faculty of MedicineAnkaraTurkey

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