title: IL2RG reversion event in a common lymphoid progenitor leads to delayed diagnosis and milder phenotype.
abstract: Severe combined immunodeficiency (SCID) is most frequently caused by mutations in the cytokine receptor common gamma chain, CD132, encoded by the X-linked gene, IL2RG. Most patients present in the first year of life with failure to thrive, severe, opportunistic infections and absence of CD3+ T cells. We present a patient with pediatric illness and a diagnosis of combined variable immune deficiency (CVID) who was diagnosed at age 23 with an inherited IL2RG mutation causing loss of signal transduction through CD132. His peripheral blood included CD3/CD4 and CD3/CD8 positive cells as well as low levels of CD19+ B cells containing a reversion to the wildtype IL2RG allele. The reversion, which was not present at birth, may account for his mild phenotype and late diagnosis.
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Laboratory of Clinical Infectious Diseases, Bethesda, MD, USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Bianca
authors.initials: B
authors.lastname: Martinez
authors.forename: Amy P
authors.initials: AP
authors.lastname: Rump
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Puck
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology*; D001987:Bronchiectasis / Q000175:diagnosis* / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D057210:Delayed Diagnosis; D006801:Humans; D007231:Infant, Newborn; D007239:Infections / Q000175:diagnosis* / Q000235:genetics; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics*; D054503:Lymphoid Progenitor Cells / Q000502:physiology*; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012867:Skin / Q000473:pathology*; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D053631:Interleukin Receptor Common gamma Subunit