An immunocompetent patient with a nonsense mutation in NHEJ1 gene

Hossein Esmaeilzadeh,
Mohammad Reza Bordbar,
Zahra Hojaji,
Parham Habibzadeh,
Dorna Afshinfar,
Mohammad MiryounesiView ORCID ID profile,
Majid Fardaei and
Mohammad Ali FaghihiEmail author

BMC Medical Genetics201920:45

https://doi.org/10.1186/s12881-019-0784-0

Received: 25 December 2018
Accepted: 13 March 2019
Published: 21 March 2019

Open Peer Review reports

Abstract

Background

DNA double-strand breaks (DSBs) are among the most deleterious types of DNA damage. DSBs are repaired by homologous recombination or non-homologous end-joining (NHEJ). NHEJ, which is central to the process of V(D)J recombination is the principle pathway for DSB repair in higher eukaryotes. Mutations in NHEJ1gene have been associated with severe combined immunodeficiency.

Case presentation

The patient was a 3.5-year-old girl, a product of consanguineous first-degree cousin marriage, who was homozygous for a nonsense mutation in NHEJ1 gene. She had initially presented with failure to thrive, proportional microcephaly as well as autoimmune hemolytic anemia (AIHA), which responded well to treatment with prednisolone. However, the patient was immunocompetent despite having this pathogenic mutation.

Conclusions

Herein, we report on a patient who was clinically immunocompetent despite having a pathogenic mutation in NHEJ1 gene. Our findings provided evidence for the importance of other end-joining auxiliary pathways that would function in maintaining genetic stability. Clinicians should therefore be aware that pathogenic mutations in NHEJ pathway are not necessarily associated with clinical immunodeficiency.