Clinical and genetic heterogeneity in Omenn syndrome and severe combined immune deficiency.
OS has been described as a clinical phenotype in infants characterized by SCID, diffuse erythroderma, and other distinct features. The pathogenesis is secondary to autologous, auto-reactive T cells produced as rare escapees from the SCID blockade. Mutations in either the RAG1 or RAG2 gene that lead to partial recombinase activity are responsible for many of the patients with these clinical features. We report on two patients, one with an atypical phenotype of OS (absence of rash but presence of other typical features) who harbored a previously undescribed mutation in RAG1, and a second who had many of the classic features of OS but was found to have a mutation in the common gamma chain (gamma(c)) cytokine receptor gene. These cases highlight the clinical and genetic heterogeneity of OS.
Gruber
Tanja A
TA
Divisions of Hematology and Oncology, Children's Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027, USA.
Shah
Ami J
AJ
Hernandez
Michelle
M
Crooks
Gay M
GM
Abdel-Azim
Hisham
H
Gupta
Sudhir
S
McKnight
Sean
S
White
Drew
D
Kapoor
Neena
N
Kohn
Donald B
DB
D016207:Cytokines / Q000235:genetics; D005076:Exanthema / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D007223:Infant; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D045567:VDJ Recombinases / Q000235:genetics
D016207:Cytokines; D018398:Homeodomain Proteins; C064658:RAG-1 protein; D045567:VDJ Recombinases