Novel NHEJ1 pathogenic variant linked to severe combined immunodeficiency, microcephaly, and abnormal T and B cell receptor repertoires.
Front Pediatr
; 10: 883173, 2022.
Article
em En
| MEDLINE
| ID: mdl-35967585
ABSTRACT
Background:
During the process of generating diverse T and B cell receptor (TCR and BCR, respectively) repertoires, double-strand DNA breaks are produced. Subsequently, these breaks are corrected by a complex system led by the non-homologous end-joining (NHEJ). Pathogenic variants in genes involved in this process, such as the NHEJ1 gene, cause severe combined immunodeficiency syndrome (SCID) along with neurodevelopmental disease and sensitivity to ionizing radiation.Objective:
To provide new clinical and immunological insights on NHEJ1 deficiency arising from a newly diagnosed patient with severe immunodeficiency. Materials andmethods:
A male infant, born to consanguineous parents, suspected of having primary immunodeficiency underwent immunological and genetic workup. This included a thorough assessment of T cell phenotyping and lymphocyte activation by mitogen stimulation tests, whole-exome sequencing (WES), TCR repertoire Vß repertoire via flow cytometry analysis, and TCR and BCR repertoire analysis via next-generation sequencing (NGS).Results:
Clinical findings included microcephaly, recurrent pneumonia, and failure to thrive. An immune workup revealed lymphopenia, reduced T cell function, and hypogammaglobulinemia. Skewed TCR Vß repertoire, TCR gamma (TRG) repertoire, and BCR repertoire were determined in the patient. Genetic analysis identified a novel homozygous missense pathogenic variant in XLF/Cernunnos c.A580Ins.T; p.M194fs. The patient underwent a successful hematopoietic stem cell transplantation (HSCT).Conclusion:
A novel NHEJ1 pathogenic variant is reported in a patient who presented with SCID phenotype that displayed clonally expanded T and B cells. An adjusted HSCT was safe to ensure full T cell immune reconstitution.
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Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article