Combined Immunodeficiency

Gene: RAG1

Green List (high evidence)

Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity
4 unrelated individuals; one mouse model
All 4 patients reported with alpha/beta T-cell lymphopaenia with gamma/delta T-cell expansion, severe CMV infection, and autoimmunity (anaemia in 3 patients and neutropaenia in 1).
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Combined cellular and humoral immune defects with granulomas
4 individuals from 3 unrelated families
Individuals presented with immunodeficiency disease with extensive granulomatous disease involving the skin, mucous membranes, and internal organs, hypogammaglobulinaemia and decreased numbers of T and B cells.
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Omenn syndrome
14 unrelated individuals; Two mouse models
Individuals typically presented with severe combined immunodeficiency associated with erythrodermia, eosinophilia, hepatosplenomegaly, lymphadenopathy, and elevated serum IgE levels.
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Severe combined immunodeficiency, B cell-negative
8 unrelated individuals; two mouse models
Individuals typically presented with failure to thrive, recurrent infections, diarrhoea and severe T cell and B cell immunodeficiency.
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Homozygous and compound heterozygous (missense, nonsense and del) variants were reported in all disease phenotypes resulting in loss of function for all disease phenotypes.
*multiple of the same variants were reported across disease phenotypes as well.

(Green for all disease phenotypes)

Created: 24 Aug 2021, 1:31 a.m. | Last Modified: 24 Aug 2021, 1:31 a.m.

Panel Version: 0.365

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity MIM# 609889; Combined cellular and humoral immune defects with granulomas MIM# 233650; Omenn syndrome MIM# 603554; Severe combined immunodeficiency, B cell-negative MIM# 601457

Publications

• 16276422
• 18463379
• 20489056
• 9630231
• 11313270
• 17476359
• 8810255
• 6823332