Diverse phenotypic and genotypic presentation of RAG1 mutations in two cases with SCID.
Severe combined immunodeficiencies (SCID) comprise a spectrum of genetic defects that involve both humoral and cellular immunities. Defects in recombinating activating gene 1 (RAG1), RAG2, Artemis, or LIG4 can disrupt V(D)J recombination. Defective V(D)J recombination of the T and B cell receptors is responsible for T(-)B(-)NK(+)SCID. Amorphic mutations in RAG1 and RAG2 cause T(-)B(-)NK(+)SCID, whereas hypomorphic mutations cause an immunodeficency characterized by oligoclonal expansion of TCRgammadelta T cells, severe CMV infection and autoimmunity. First patient is a typical T(-)B(-)NK(+)SCID with clinical and immunologic findings while the second is atypical with normal immunoglobulin levels, CD4 lymphopenia, elevated TCRgammadelta T cells, persistent CMV infection, and autoimmune hemolytic anemia. These cases are presented to emphasize that mutations in RAG1 gene may lead to a diverse spectrum of clinical and immunologic findings while hypomorphic mutations may be related with autoimmunity and refractory CMV infection during infancy.
Karaca
Neslihan Edeer
NE
Department of Pediatrics, Faculty of Medicine, Ege University, 35100, Bornova, Izmir, Turkey. neslihanedeer@yahoo.com
Aksu
Guzide
G
Genel
Ferah
F
Gulez
Nesrin
N
Can
Sema
S
Aydinok
Yesim
Y
Aksoylar
Serap
S
Karaca
Emin
E
Altuglu
Imren
I
Kutukculer
Necil
N
D002648:Child; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology / Q000628:therapy; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology / Q000628:therapy; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000628:therapy
D018398:Homeodomain Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C064658:RAG-1 protein