Abstract | BACKGROUND: METHODS: STAT1 was sequenced in 3 patients with PML. U3C cell lines were transfected with STAT1 and assays to search for STAT1 phosphorylation, transcriptional response, and target gene expression were performed. RESULTS: We identified 3 new unrelated cases of PML in patients with GOF STAT1 mutations, including the novel STAT1 mutation, L400Q. These STAT1 mutations caused delayed STAT1 dephosphorylation and enhanced interferon-gamma-driven responses. In our review of the literature regarding PML in primary immune deficiencies we found 26 cases, only 54% of which were molecularly characterized, the remainder being syndromically diagnosed only. CONCLUSIONS: The occurrence of PML in 4 cases of STAT1 GOF suggests that STAT1 plays a critical role in the control of JC virus in the central nervous system.
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Authors | Christa S Zerbe, Beatriz E Marciano, Rohit K Katial, Carah B Santos, Nick Adamo, Amy P Hsu, Mary E Hanks, Dirk N Darnell, Martha M Quezado, Cathleen Frein, Lisa A Barnhart, Victoria L Anderson, Gulbu Uzel, Alexandra F Freeman, Andrea Lisco, Avindra Nath, Eugene O Major, Elizabeth P Sampaio, Steven M Holland |
Journal | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
(Clin Infect Dis)
Vol. 62
Issue 8
Pg. 986-94
(Apr 15 2016)
ISSN: 1537-6591 [Electronic] United States |
PMID | 26743090
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Review)
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Copyright | Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US. |
Chemical References |
- STAT1 Transcription Factor
- STAT1 protein, human
- Interferon-gamma
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Topics |
- Adult
- Brain
(diagnostic imaging)
- Cell Line, Tumor
- Female
- Gene Expression Regulation
- Humans
- Immunologic Deficiency Syndromes
(complications, diagnostic imaging, genetics)
- Interferon-gamma
(pharmacology)
- JC Virus
(growth & development)
- Leukoencephalopathy, Progressive Multifocal
(complications, diagnostic imaging, genetics, immunology)
- Male
- Middle Aged
- Mutation
- STAT1 Transcription Factor
(genetics, physiology)
- Sequence Analysis, DNA
- Transcriptional Activation
- Viral Load
- Young Adult
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