RAG-deficient severe combined immunodeficiency (RAG-SCID)

Contact details Introduction Molecular Genetics Service RAG-deficient severe combined immunodeficiency (RAG-SCID, MIM 601457) is an Level 6, Barclay House autosomal recessive immunodeficiency characterised by a lack of circulating T and B 37 Queen Square cells. Affected individuals can be diagnosed on the basis of an abnormality or London, WC1N 3BH deficiency of the V(D)J recombinase subunits, RAG1 and RAG2. The RAG1 and T +44 (0) 20 7762 6888 RAG2 genes have 2 exons of which exon 2 is coding. Family specific mutations have F +44 (0) 20 7813 8578 been found throughout the coding region of both genes. Omenn syndrome (MIM 603554) is a leaky TlowB-SCID characterised by reticuloendotheliosis and eosinophilia. It is caused by mutations in RAG1 and RAG2 that result in a partially Samples required functional recombinase.  5ml venous blood in plastic EDTA bottles (>1ml from neonates) Referrals  Prenatal testing must be arranged  Patients with suspected RAG-SCID. in advance, through a Clinical  Carrier testing can be offered to the relatives of RAG-SCID or Omenn Genetics department if possible. syndrome patients once a disease-causing mutation has been identified.  Amniotic fluid or CV samples However, due to the rarity of the disorder, partner screening is not offered should be sent to Cytogenetics for unless there is consanguinity or a family history of RAG-SCID or Omenn dissecting and culturing, with instructions to forward the sample syndrome in the partner. to the Regional Molecular Genetics  RAG1 and RAG2 protein analysis can be performed by the Molecular laboratory for analysis Immunology laboratory at GOSH but requires a bone marrow sample from  A completed DNA request card affected patients. This requires prior arrangement and completion of specific should accompany all samples request forms (see contact information below). Prenatal testing Patient details To facilitate accurate testing and Prenatal testing is available for families in whom specific mutations have been reporting please provide patient identified or in whom appropriate family studies have been undertaken. Please demographic details (full name, date of contact the laboratory to discuss. birth, address and ethnic origin), details of any relevant family history and full Service offered contact details for the referring clinician Mutation screening of the RAG1 and RAG2 genes in affected individuals. Due to the requirement of a bone marrow sample for protein analysis, mutation screening will be carried out in the absence of protein testing if clinically indicated. If DNA from the affected individual is unavailable then screening can be undertaken in the parents. Technical Mutation screening is undertaken by sequence analysis of the RAG1 and RAG2 genes. Target reporting time 8 weeks for routine mutation screen in index case. 2 weeks for carrier testing using mutation-specific tests. For urgent samples please contact the laboratory. To arrange RAG expression studies please contact Dr Kimberly Gilmour, Molecular Immunology, GOSH Tel: +44 (0) 20 7829 8835, Email: [email protected]

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