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
