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A partial form of recessive STAT1 deficiency in humans

Chapgier, Ariane ; Kong, Xiao-Fei ; Boisson-Dupuis, Stéphanie ; Jouanguy, Emmanuelle ; Averbuch, Diana ; Feinberg, Jacqueline ; Zhang, Shen-Ying ; Bustamante, Jacinta ; Vogt, Guillaume ; Lejeune, Julien ; Mayola, Eleonore ; de Beaucoudrey, Ludovic ; Abel, Laurent ; Engelhard, Dan ; Casanova, Jean-Laurent

The Journal of clinical investigation, 2009-06, Vol.119 (6), p.1502-1514 [Periódico revisado por pares]

United States: American Society for Clinical Investigation

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Título:
A partial form of recessive STAT1 deficiency in humans
Autor: Chapgier, Ariane ; Kong, Xiao-Fei ; Boisson-Dupuis, Stéphanie ; Jouanguy, Emmanuelle ; Averbuch, Diana ; Feinberg, Jacqueline ; Zhang, Shen-Ying ; Bustamante, Jacinta ; Vogt, Guillaume ; Lejeune, Julien ; Mayola, Eleonore ; de Beaucoudrey, Ludovic ; Abel, Laurent ; Engelhard, Dan ; Casanova, Jean-Laurent
Assuntos: Alleles ; Alternative Splicing - genetics ; Amino Acids - genetics ; Amino Acids - metabolism ; Base Sequence ; Cells, Cultured ; DNA binding proteins ; Female ; Genetic aspects ; Genetic transcription ; Humans ; Immunodeficiency ; Interferon ; Interferons - genetics ; Interferons - metabolism ; Male ; Mutation - genetics ; Pedigree ; Physiological aspects ; Risk factors ; RNA, Messenger - genetics ; Siblings ; STAT1 Transcription Factor - deficiency ; STAT1 Transcription Factor - genetics ; STAT1 Transcription Factor - metabolism
É parte de: The Journal of clinical investigation, 2009-06, Vol.119 (6), p.1502-1514
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Complete STAT1 deficiency is an autosomal recessive primary immunodeficiency caused by null mutations that abolish STAT1-dependent cellular responses to both IFN-alpha/beta and IFN-gamma. Affected children suffer from lethal intracellular bacterial and viral diseases. Here we report a recessive form of partial STAT1 deficiency, characterized by impaired but not abolished IFN-alpha/beta and IFN-gamma signaling. Two affected siblings suffered from severe but curable intracellular bacterial and viral diseases. Both were homozygous for a missense STAT1 mutation: g.C2086T (P696S). This STAT1 allele impaired the splicing of STAT1 mRNA, probably by disrupting an exonic splice enhancer. The misspliced forms were not translated into a mature protein. The allele was hypofunctional, because residual full-length mRNA production resulted in low but detectable levels of normally functional STAT1 proteins. The P696S amino acid substitution was not detrimental. The patients' cells, therefore, displayed impaired but not abolished responses to both IFN-alpha and IFN-gamma. We also show that recessive STAT1 deficiencies impaired the IL-27 and IFN-lambda1 signaling pathways, possibly contributing to the predisposition to bacterial and viral infections, respectively. Partial recessive STAT1 deficiency is what we believe to be a novel primary immunodeficiency, resulting in impairment of the response to at least 4 cytokines (IFN-alpha/beta, IFN-gamma, IFN-lambda1, and IL-27). It should be considered in patients with unexplained, severe, but curable intracellular bacterial and viral infections.
Editor: United States: American Society for Clinical Investigation
Idioma: Inglês

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A partial form of recessive STAT1 deficiency in humans

United States: American Society for Clinical Investigation

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