Genetic heterogeneity for a Nijmegen breakage-like syndrome

Paola Maraschio, E. Spadoni, C. Tanzarella, A. Antoccia, A. di Masi, M. Maghnie, R. Varon, I. Demuth, L. Tiepolo, C. Danesino

Research output: Contribution to journalArticlepeer-review


Nijmegen breakage syndrome (NBS) is a rare, autosomal-recessive chromosome instability disorder characterized by growth and developmental defects, immunodeficiency, high susceptibility to lymphoid malignancies, hypersensitivity to ionizing radiation and aberrant cell-cycle checkpoint control. The disease is caused by mutations in the NBS1 gene, which encodes nibrin, a component of the hMre11-Rad50-p95 complex involved in cellular response to DNA double-strand breaks. Genetic heterogeneity has been suggested in at least two patients with the NBS phenotype, but no mutation in the NBS1 gene; recently, mutations in the gene encoding the enzyme ligase IV have been identified in patients with signs of NBS. We describe a boy with an NBS clinical phenotype but no mutation in either the NBS1 or the LIG4 genes. The analysis of his cellular phenotype reveals chromosome instability and radiosensitivity, but normal cell-cycle checkpoint control. In addition, a literature review was carried out to summarize and compare data of all NBS-like patients reported to date. This case confirms genetic heterogeneity for NBS. We believe that dissecting the clinical and cellular phenotypes of this and other NBS-like patients will provide useful information for the research of new genes involved in cellular response to DNA damage and the assessment of cancer risk in NBS-like syndrome.

Original languageEnglish
Pages (from-to)283-290
Number of pages8
JournalClinical Genetics
Issue number4
Publication statusPublished - Apr 1 2003


  • DNA damage response
  • LIG4
  • NBS-like
  • Nijmegen breakage syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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