Mutations of recombination activating gene (RAG) 1/2 in humans are associated with a distinct and broad clinical phenotypes reach from severe combined immunodeficiency (SCID) to Omenn syndrome or a combined immunodeficiency with autoimmunity. To define clinical heterogeneity of RAG2 G35A mutation, in families of different origin.
A next-generation sequencing of 200 genes associated with primary immunodeficiency identified RAG2 G35A mutation.
We present three patients with RAG2 G35A mutation in two distinct families. Two years old male of Arab origin with homozygous mutation was diagnosed as T-B-NK+ SCID. His male sibling with heterozygous mutation was diagnosed as a leaky SCID and they are doing well with regular IVIG therapy. The third patient with a leaky SCID phenotype was Turkish and died because of severe hemophagocytic syndrome.
Clinical heterogeneity of these three patients and also their parents with the same RAG mutation was striking. Clinical heterogeneity of any specific mutation of RAG2 should be related to the environmental factors.