# LIG4 syndrome

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> Source: https://en.wikipedia.org/wiki/LIG4_syndrome
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{{Infobox medical condition (new)
| name            = LIG4 syndrome
| synonyms        =  Ligase IV syndrome
| image           = LIG4.jpg
| caption         = Person at age 12 showing dysmorphic features
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'''LIG4 syndrome''' or '''ligase IV syndrome''' is an extremely rare condition caused by mutations in the [DNA ligase IV](/source/LIG4) (LIG4) gene. Some mutations in this gene are associated with a resistance against [multiple myeloma](/source/multiple_myeloma) and [severe combined immunodeficiency](/source/severe_combined_immunodeficiency).<ref>{{cite web|title=LIGASE IV, DNA, ATP-DEPENDENT; LIG4|url=http://omim.org/entry/601837|work=OMIM|access-date=2 January 2012}}</ref> Severity of symptoms depends on the degree of reduced enzymatic activity of Ligase IV or gene expression.  [Ligase IV](/source/LIG4) is a critical component of the [non-homologous end joining](/source/non-homologous_end_joining) (NHEJ) mechanism that repairs [DNA double-strand breaks](/source/DNA_damage_(naturally_occurring)).<ref name="pmid27717373">{{cite journal |vauthors=Altmann T, Gennery AR |title=DNA ligase IV syndrome; a review |journal=Orphanet J Rare Dis |volume=11 |issue=1 |pages=137 |date=October 2016 |pmid=27717373 |pmc=5055698 |doi=10.1186/s13023-016-0520-1 |doi-access=free }}</ref>  It is employed in repairing DNA double-strand breaks caused by [reactive oxygen species](/source/reactive_oxygen_species) produced by normal metabolism, or by DNA damaging agents such as [ionizing radiation](/source/ionizing_radiation).  NHEJ is also used to repair the DNA double-strand break intermediates that occur in the production of T and B [lymphocyte](/source/lymphocyte) receptors.{{citation needed|date=November 2020}}

As DNA ligase IV is essential in [V(D)J recombination](/source/V(D)J_recombination), the mechanism by which [immunoglobulins](/source/immunoglobulins), [B cell](/source/B_cell_receptor) and [T cell receptor](/source/T_cell_receptor)s are formed, patients with LIG4 syndrome may have less effective or defective V(D)J recombination. Some patients have a severe immunodeficiency characterized by [pancytopenia](/source/pancytopenia), causing chronic [respiratory infections](/source/respiratory_infections) and sinusitis.<ref name="O'Driscoll2001">{{cite journal|title=DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency|journal=Mol Cell|year=2001|volume=8|pages=1175–85|pmid=11779494|vauthors=O'Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P|issue=6|doi=10.1016/S1097-2765(01)00408-7|doi-access=free}}</ref> Clinical features also include [Seckel syndrome](/source/Seckel_syndrome)-like facial abnormalities and [microcephaly](/source/microcephaly). Patients also have [growth retardation](/source/growth_retardation) and skin conditions, including [photosensitivity](/source/Photosensitivity_in_humans), [psoriasis](/source/psoriasis) and [telangiectasia](/source/telangiectasia). Although not present in all, patients may also present with [hypothyroidism](/source/hypothyroidism) and [type II diabetes](/source/type_II_diabetes) and possibly malignancies such as [acute T-cell leukemia](/source/T-cell_leukemia).<ref name="O'Driscoll2001" /><ref name=Ben-Omran2005>{{cite journal|title=A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome|journal=Am J Med Genet A|year=2005|volume=137A|pages=283–7|pmid=16088910|vauthors=Ben-Omran TI, Cerosaletti K, Concannon P, Weitzman S, Nezarati MM|doi=10.1002/ajmg.a.30869|issue=3|s2cid=12823417|doi-access=free}}</ref> The clinical phenotype of LIG4 syndrome closely resembles that of [Nijmegen breakage syndrome](/source/Nijmegen_breakage_syndrome) (NBS).{{citation needed|date=November 2020}}

== See also ==
* [LIG4](/source/LIG4)
* [List of cutaneous conditions](/source/List_of_cutaneous_conditions)

== References ==
{{reflist}}

== External links ==
{{Medical resources
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| ICD10           = D81.1
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| OMIM            = 606593
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| MeshID          = C564694
| Orphanet        = 99812
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Category:Noninfectious immunodeficiency-related cutaneous conditions
Category:Rare syndromes
Category:Syndromes with microcephaly

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Adapted from the Wikipedia article [LIG4 syndrome](https://en.wikipedia.org/wiki/LIG4_syndrome) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/LIG4_syndrome?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.