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LIG4 syndrome

MIM.606593 13q22-q34

Wednesday 19 November 2003

DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4). The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi disease (Fanconi anemia).

Synopsis

- immunodeficiency
- developmental and growth delay
- unusual facial features
- microcephaly
- pancytopenia
- bone marrow failure (#17224058#)
- skin anomalies

Differential diagnosis

- DNA damage response diseases

  • Nijmegen breakage syndrome (MIM.251260)
  • Seckel syndrome
  • Fanconi disease (Fanconi anemia)

Etiology

- mutations in the LIG4 gene coding for DNA ligase 4at 13q22-q34 (MIM.601837)

References

- Buck D, Moshous D, de Chasseval R, Ma Y, le Deist F, Cavazzana-Calvo M, Fischer A, Casanova JL, Lieber MR, de Villartay JP. Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV. Eur J Immunol. 2006 Jan;36(1):224-35. PMID: #16358361#

- Revy P, Buck D, le Deist F, de Villartay JP. The repair of DNA damages/modifications during the maturation of the immune system: lessons from human primary immunodeficiency disorders and animal models. Adv Immunol. 2005;87:237-95. PMID: #16102576#

- Ben-Omran, T. I.; Cerosaletti, K.; Concannon, P.; Weitzman, S.; Nezarati, M. M. : A patient with mutations in DNA ligase IV: clinical features and overlap with Nijmegen breakage syndrome. Am. J. Med. Genet. 137A: 283-287, 2005. PMID: #16088910#

- O’Driscoll, M.; Cerosaletti, K. M.; Girard, P.-M.; Dai, Y.; Stumm, M.; Kysela, B.; Hirsch, B.; Gennery, A.; Palmer, S. E.; Seidel, J.; Gatti, R. A.; Varon, R.; Oettinger, M. A.; Neitzel, H.; Jeggo, P. A.; Concannon, P. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Molec Cell 8: 1175-1185, 2001. PubMed ID : #11779494#