Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation;
NHEJ1 syndrome

Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation is a syndrome associated with T and B cell-combined lymphocytopenia, growth retardation, microcephaly, and increased cellular radiosensitivity. Mutations in human NHEJ1 can lead to lymphocytopenia due to its role in V(D)J recombination in the immune system. This disease shows features common with the ones observed in LIG4 deficiency or Nijmegen breakage syndrome.

Primary immunodeficiency

NHEJ1 [HSA:79840] [KO:K10980]

LIG4 deficiency and Nijmegen breakage syndrome are described in H00094.

PMID:16439204 (description, gene)

Buck D, Malivert L, de Chasseval R, Barraud A, Fondaneche MC, Sanal O, Plebani A, Stephan JL, Hufnagel M, le Deist F, Fischer A, Durandy A, de Villartay JP, Revy P

Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly.

Cell 124:287-99 (2006)

PMID:20597108 (description, gene)

Dutrannoy V, Demuth I, Baumann U, Schindler D, Konrat K, Neitzel H, Gillessen-Kaesbach G, Radszewski J, Rothe S, Schellenberger MT, Nurnberg G, Nurnberg P, Teik KW, Nallusamy R, Reis A, Sperling K, Digweed M, Varon R

Clinical variability and novel mutations in the NHEJ1 gene in patients with a Nijmegen breakage syndrome-like phenotype.

Hum Mutat 31:1059-68 (2010)

PMID:19223975 (description, gene)

Schwartz M, Oren YS, Bester AC, Rahat A, Sfez R, Yitzchaik S, de Villartay JP, Kerem B

Impaired replication stress response in cells from immunodeficiency patients carrying Cernunnos/XLF mutations.

PLoS One 4:e4516 (2009)

PMID:16439205 (description)

Ahnesorg P, Smith P, Jackson SP

XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining.

Cell 124:301-13 (2006)