Cernunnos/XLF Deficiency: A Syndromic Primary Immunodeficiency

Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1) was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases. 1. Introduction Severe combined immunodeficiency (SCID) is defined as a group of disorders that affect both humoral and cellular immunity. Two groups of SCID have been defined: B(+) SCID (with residual B cells) and B(？) SCID (with absence of B cells) [1]. Approximately 35% of all SCIDs are radiosensitive and 4 proteins and responsible genes (DCLRE1C gene for Artemis, LIG4 gene for DNA ligase IV, PRKDC gene for DNA protein kinase catalytic subunit, and NHEJ1 gene for Cernunnos) in nonhomologous end joining pathways have been identified as responsible genes [1, 2]. DNA ligase IV and Cernunnos deficiency lead to microcephaly and, additionally, severe growth retardation [2]. Here, we present a 3-year-old girl admitted with severe growth retardation, recurrent perianal abscess, polydactyly, and pancytopenia. Low immunoglobulin (Ig)G, IgA levels, normal IgM levels, and agammaglobulinemia were detected and Cernunnos/XLF gene mutation was subsequently identified. 2. A Case Report Three-year-old girl was transferred to our clinic for consultation because of growth retardation, pancytopenia, and recurrent perianal abscess. Her parents were consanguineous and two of her mother’s siblings had died because of infections in early infancy without definitive diagnosis in her family history.