RAG Mutations in Human B Cell-Negative SCID

• DOI: 10.1126/science.274.5284.97
• Publication Date: 2002-07-27T09:50:14Z
• Authors: Klaus Schwarz; George H. Gauss; Leopold Ludwig; Ulrich Pannicke; Zhong Li; Doris Lindner; Wilhelm Friedrich; Reinhard A. Seger; Thomas E. Hansen-...; Stephen Desiderio; Michael R. Lieber; Claus R. Bartram
• Keywords: Homeodomain Proteins; Male; Recombination, Genetic; 0301 basic medicine; B-Lymphocytes; Genes, Immunoglobulin; Receptors, Antigen, T-Cell; Nuclear Proteins; Proteins; Genes, Recessive; Transfection; Cell Line; Immunophenotyping; 3. Good health; DNA-Binding Proteins; Consanguinity; 03 medical and health sciences; Mutation; Humans; Female; Severe Combined Immunodeficiency; Polymorphism, Single-Stranded Conformational; Sequence Deletion

Patients with human severe combined immunodeficiency (SCID) can be divided into those with B lymphocytes (B + SCID) and those without (B − SCID). Although several genetic causes are known for B + SCID, the etiology of B − SCID has not been defined. Six of 14 B − SCID patients tested were found to carry a mutation of the recombinase activating gene 1 ( RAG-1 ), RAG-2 , or both. This mutation resulted in a functional inability to form antigen receptors through genetic recombination and links a defect in one of the site-specific recombination systems to a human disease.