A Novel Missense LIG4 Mutation in a Patient With a Phenotype Mimicking Behcet's Disease


Taskiran E. Z. , SÖNMEZ H. E. , KOŞUKCU C., Tavukcuoglu E., YAZICI G., ESENDAĞLI G., ...More

JOURNAL OF CLINICAL IMMUNOLOGY, vol.39, no.1, pp.99-105, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 1
  • Publication Date: 2019
  • Doi Number: 10.1007/s10875-018-0587-7
  • Title of Journal : JOURNAL OF CLINICAL IMMUNOLOGY
  • Page Numbers: pp.99-105

Abstract

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 Behcet'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.