Yazdani Reza, Abolhassani Hassan, Tafaroji Javad, Azizi Gholamreza, Hamidieh Amir Ali, Chou Janet, Geha Raif S, Aghamohammadi Asghar
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Molecular Immunology Interest Group (MIIG), Universal Scientific Education and Research Network (USERN), Isfahan, Iran.
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Clin Immunol. 2017 Oct;183:201-206. doi: 10.1016/j.clim.2017.07.007. Epub 2017 Jul 17.
Non-homologous end-joining (NHEJ) is a pathway that repairs double-strand breaks (DSB) in DNA and plays a vital role in V(D)J recombination of immunoglobulin genes. Cernunnos is a DNA repair factor that is involved in nonhomologous end-joining (NHEJ) process. Impairment in Cernunnos leads to a genetic disease characterized by neural disorders, immunodeficiency and increased radiosensitivity. We herein describe a severe combined immunodeficiency (SCID) patient with T- B+ phenotype who had a mutation in Cernunnos gene and manifested recurrent infections, microcephaly and growth retardation with hypogammaglobulinemia. Furthermore, our patient was associated with BCG adenitis and autoimmunity that less is observed in patients with Cernunnos deficiency. In contrast to previous reported Cernunnos-deficient patients, our patient had normal B-cell number along with normal IgA and IgM, suggesting a leaky form of the Cernunnos deficiency due to residual count of B cells in our patient. Cernunnos deficiency should be considered in children with recurrent bacterial infections, microcephaly and growth retardation, in spite of having normal B-cell as well as normal IgM and IgA level.
非同源末端连接（NHEJ）是一种修复DNA双链断裂（DSB）的途径，在免疫球蛋白基因的V（D）J重组中起着至关重要的作用。Cernunnos是一种参与非同源末端连接（NHEJ）过程的DNA修复因子。Cernunnos功能受损会导致一种以神经紊乱、免疫缺陷和辐射敏感性增加为特征的遗传疾病。我们在此描述了一名患有T-B+表型的严重联合免疫缺陷（SCID）患者，该患者Cernunnos基因发生突变，表现为反复感染、小头畸形、生长发育迟缓伴低丙种球蛋白血症。此外，我们的患者还伴有卡介苗腺炎和自身免疫，这在Cernunnos缺陷患者中较少见。与先前报道的Cernunnos缺陷患者不同，我们的患者B细胞数量正常，IgA和IgM水平也正常，提示由于患者体内B细胞的残留数量，该患者存在一种Cernunnos缺陷的渗漏形式。对于反复发生细菌感染、小头畸形和生长发育迟缓的儿童，尽管其B细胞以及IgM和IgA水平正常，也应考虑Cernunnos缺陷的可能性。
