Cernunnos deficiency: Further delineation in 5 Egyptian patients

Rabab El Hawary; Safa Meshaal; Sohilla Lotfy; Dalia Abd Elaziz; Radwa Alkady; Alia Eldash; Aya Erfan; Engy Chohayeb; Mai Saad; Rania Darwish; Jeannette Boutros; Nermeen Galal; Aisha Elmarsafy

doi:10.1016/j.ejmg.2023.104840

Cernunnos deficiency: Further delineation in 5 Egyptian patients

Eur J Med Genet. 2023 Oct;66(10):104840. doi: 10.1016/j.ejmg.2023.104840. Epub 2023 Sep 11.

Authors

Affiliations

¹ Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Electronic address: rabab.elhawary@kasralainy.edu.eg.
² Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
³ Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.

PMID: 37703920
DOI: 10.1016/j.ejmg.2023.104840

Abstract

Cernunnos deficiency is a rare genetic disorder characterized by immunodeficiency, microcephaly, growth retardation, bird-like facies, sensitivity to ionizing radiation, few autoimmune manifestations, premature aging of hematopoietic stem cells at an early age, and occasional myeloproliferative disease. Herein we present five Egyptian Cernunnos patients from 3 different families. We describe the patients' clinical phenotypes, their immunological profile as well as genetic results. Sequence analysis revealed three different mutations in the NHEJ1 gene: a nonsense variant c.532C > T; p.(Arg178Ter), an intronic variant c.178-1G > A and a frameshift insertion variant c.233dup; p.(Asn78LysfsTer14). In conclusion, Cernunnos deficiency can have a wide range of clinical features. The characteristic immune profile including a decrease in recent thymic emigrants and naive T cells, markedly elevated memory T cells together with normal to high IgM, and a decrease in IgG and IgA. This immune profile is highly suggestive of Cernunnos deficiency in T-B-NK + SCID patients especially surviving for older ages.

Keywords: Cernunnos; Inborn errors of immunity; NHEJ1 gene; Severe combined immunodeficiency.