CD3ε gene variant causing typical SCID and Omenn syndrome in patients from two unrelated families

Abstract

Severe combined immune deficiencies (SCIDs) are a group of rare diseases that impact the immune system. Depending on the underlying gene defects, SCIDs exhibit various clinical and immunological phenotypes. Multiple gene defects have been linked to the presentation of SCIDs, including typical SCIDs and Omenn syndrome. Typical SCIDs manifest early in life with recurrent infections caused by opportunistic pathogens. Omenn syndrome is characterized by a clinical triad of erythroderma, hepatosplenomegaly, and lymphadenopathy, commonly accompanied by peripheral eosinophilia and elevated IgE levels. Here, we present two unrelated families (2 siblings & one patient from a different family), all of the same ethnicity and race, who presented with variable clinical and laboratory presentations of severe combined immunodeficiency (SCID) while harboring the same missense, homozygous variant in the CD3ε gene (P.Gly94Ala), previously classified as a variant of unknown significance. Our case series shows a potentially disease-causing variant that was previously classified as a variant of unknown significance, in addition to suggesting a treatment for Omenn syndrome-related immune dysregulation using corticosteroids as a monotherapy. We concluded that a defect in the CD3ε gene can result in classical SCID, along with features of Omenn syndrome that may arise from this genetic defect. A heightened level of suspicion is crucial for diagnosing SCID cases, as various presentations can emerge from the same genetic variant.

References

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