LIG4 syndrome

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LIG4 syndrome
Classification and external resources
OMIM 606593

LIG4 syndrome (also known as Ligase IV syndrome) is an extremely rare condition caused by mutations in the DNA Ligase IV (LIG4) gene. Some mutations in this gene are associated with a resistance against multiple myeloma and Severe Combined Immunodeficiency.[1] Severity of symptoms depends on the degree of reduced enzymatic activity of Ligase IV or gene expression.

As DNA ligase IV is essential in V(D)J recombination, the mechanism by which immunoglobulins, B cell and T cell receptors are formed, patients with LIG4 syndrome may suffer from less effective or defective V(D)J recombination. Some patients have a severe immunodeficiency characterized by pancytopenia, causing chronic respiratory infections and sinusitis.[2] Clinical features also include Seckel syndrome-like facial abnormalities and microcephaly. Patients also suffer from growth retardation and skin conditions, including photosensitivity, psoriasis and telangiectasia. Although not present in all, patients may also present with hypothyroidism and type II diabetes and possibly malignancies such as acute T-cell leukemia.[2][3] The clinical phenotype of LIG4 syndrome closely resembles that of Nijmegen breakage syndrome (NBS).

See also[edit]

References[edit]

  1. ^ "LIGASE IV, DNA, ATP-DEPENDENT; LIG4". OMIM. Retrieved 2 January 2012. 
  2. ^ a b 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 (2001). "DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency". Mol Cell. 8: 1175–85. doi:10.1016/S1097-2765(01)00408-7. PMID 11779494. 
  3. ^ Ben-Omran TI, Cerosaletti K, Concannon P, Weitzman S, Nezarati MM (2005). "A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome". Am J Med Genet A. 137A (3): 283–7. doi:10.1002/ajmg.a.30869. PMID 16088910.