Novel STAT1 alleles in a patient with impaired resistance to mycobacteria.
Partial defects in interferon (IFN)-γ signaling lead to susceptibility to infections with nontuberculous mycobacteria. The receptors for IFN-α and IFN-γ activate components of the Janus kinase-signal transducer and activator of transcription (STAT) signaling pathway. Some defects in STAT1 mainly affect IFN-γ signaling, thus resulting in mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a severe disease but patients show a favorable response to anti-mycobacterial chemotherapy. Other defects in STAT1 affect both IFN-α and IFN-γ signaling resulting in mycobacterial and lethal viral disease. We report here a patient with two novel STAT1 alleles, which in combination results in a recessive trait with partial STAT1 deficiency and mycobacterial disease. Cells from the patient did respond to mycobacterial antigen, but both the expression of STAT1 and phosphorylation of STAT1 in response to IFN-γ treatment were reduced. This is the first report of a mutation in the N-terminal part of STAT1 involved in causing mycobacterial disease.
Department of Pediatrics, Copenhagen University Hospital, Rigshospitalet, Denmark.
Ines Ackerl
IA
Kristensen
Jens Erik
JE
Veirum
Bjarne Kuno
BK
Møller
Mette
M
Christiansen
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000293:Adolescent; D000483:Alleles; D001483:Base Sequence; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D056726:Genetic Association Studies; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007371:Interferon-gamma / Q000494:pharmacology; D016131:Lymphocyte Subsets / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009161:Mycobacterium / Q000276:immunology; D009164:Mycobacterium Infections / Q000235:genetics*; D019081:O Antigens / Q000276:immunology; D010375:Pedigree; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000276:immunology; D017471:Receptors, Interferon / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D000096743:Interferon gamma Receptor
D000276:Adjuvants, Immunologic; D007371:Interferon-gamma; D019081:O Antigens; D012333:RNA, Messenger; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human