An immunocompetent patient with a nonsense mutation in NHEJ1 gene.
Autoimmune hemolytic Anemia
Genetic disorders
Immunologic deficiency syndromes
Nonhomologous end-joining factor 1, human
Severe combined immunodeficiency
Journal
BMC medical genetics
ISSN: 1471-2350
Titre abrégé: BMC Med Genet
Pays: England
ID NLM: 100968552
Informations de publication
Date de publication:
21 03 2019
21 03 2019
Historique:
received:
25
12
2018
accepted:
13
03
2019
entrez:
23
3
2019
pubmed:
23
3
2019
medline:
21
8
2019
Statut:
epublish
Résumé
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 NHEJ1 gene have been associated with severe combined immunodeficiency. 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. 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.
Sections du résumé
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 NHEJ1 gene 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.
Identifiants
pubmed: 30898087
doi: 10.1186/s12881-019-0784-0
pii: 10.1186/s12881-019-0784-0
pmc: PMC6429708
doi:
Substances chimiques
Codon, Nonsense
0
DNA-Binding Proteins
0
NHEJ1 protein, human
0
DNA Repair Enzymes
EC 6.5.1.-
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
45Subventions
Organisme : NINDS NIH HHS
ID : R01 NS081208
Pays : United States
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