IL2RG – Omenn syndrome

X-linked IL2RG mutations have been identified in male infants presenting with Omenn syndrome (OS), a variant of severe combined immunodeficiency characterized by erythroderma, alopecia, lymphadenopathy, hepatosplenomegaly, eosinophilia and hypogammaglobulinemia. A single case report described a novel IL2RG in-frame deletion c.337_339del (p.Ser113del) in a 7-month-old boy with OS features and low NK⁺B⁺ phenotype, who responded to umbilical cord blood transplant (PMID:31456262). In a retrospective series of 21 SCID and 6 OS patients, IL2RG variants were found in 3 male OS cases with positive X-linked family history, confirming X-linked recessive inheritance and segregation in one extended pedigree (PMID:24481607). Functional assays of IL2RG point and frameshift mutants have consistently shown loss of cytokine binding and signal transduction, supporting a haploinsufficiency mechanism (PMID:8027558). No studies have refuted this gene–disease link. Genetic testing for IL2RG should be considered in male infants with Omenn syndrome to enable early diagnosis and prompt hematopoietic stem cell transplantation.

Key take-home: X-linked IL2RG deficiency underlies a variant Omenn syndrome and has clear diagnostic and therapeutic implications.

References

• The Journal of dermatology • 2019 • Prominent dermal Langerhans cells in an Omenn syndrome patient with a novel mutation in the IL2RG gene. PMID:31456262
• Journal of clinical immunology • 2014 • Severe combined immunodeficiency in Serbia and Montenegro between years 1986 and 2010: a single-center experience. PMID:24481607
• Journal of immunology • 1994 • Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency. PMID:8027558

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