Estimated disease incidence of RAG1/2 mutations: A case report and querying the Exome Aggregation Consortium

RAG deficiency is emerging as one of the leading causes of SCID and leaky SCID with an estimated incidence of 1:336,000. Hypomorphic mutations in the RAG genes can also lead to highly variable delayed-onset combined immunodeficiency diseases. We estimate the population genetic frequency of these hypomorphic diseases as up to 1:181,000, suggesting that RAG1/2 mutations are likely to contribute to undiagnosed cases of combined immunodeficiencies.