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DNA ligase IV syndrome; a review

Lookup NU author(s): Dr Tom Altmann, Professor Andrew GenneryORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


DNA ligase IV deficiency is a rare primary immunodeficiency, LIG4 syndrome, often associated with other systemic features. DNA ligase IV is part of the non-homologous end joining mechanism, required to repair DNA double stranded breaks. Ubiquitously expressed, it is required to prevent mutagenesis and apoptosis, which can result from DNA double strand breakage caused by intracellular events such as DNA replication and meiosis or extracellular events including damage by reactive oxygen species and ionising radiation.Within developing lymphocytes, DNA ligase IV is required to repair programmed DNA double stranded breaks induced during lymphocyte receptor development.Patients with hypomorphic mutations in LIG4 present with a range of phenotypes, from normal to severe combined immunodeficiency. All, however, manifest sensitivity to ionising radiation. Commonly associated features include primordial growth failure with severe microcephaly and a spectrum of learning difficulties, marrow hypoplasia and a predisposition to lymphoid malignancy. Diagnostic investigations include immunophenotyping, and testing for radiosensitivity. Some patients present with microcephaly as a predominant feature, but seemingly normal immunity. Treatment is mainly supportive, although haematopoietic stem cell transplantation has been used in a few cases.

Publication metadata

Author(s): Altmann T, Gennery AR

Publication type: Review

Publication status: Published

Journal: Orphanet Journal of Rare Diseases

Year: 2016

Volume: 11

Online publication date: 07/10/2061

Acceptance date: 27/09/2016

ISSN (electronic): 1750-1172



DOI: 10.1186/s13023-016-0520-1