دورية أكاديمية
Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma
| العنوان: | Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma |
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| المؤلفون: | Byun, Minji, Abhyankar, Avinash, Lelarge, Virginie, Plancoulaine, Sabine, Palanduz, Ayse, Telhan, Leyla, Boisson, Bertrand, Picard, Capucine, Dewell, Scott, Zhao, Connie, Jouanguy, Emmanuelle, Feske, Stefan, Abel, Laurent, Casanova, Jean-Laurent |
| المصدر: | Journal of Experimental Medicine ; volume 207, issue 11, page 2307-2312 ; ISSN 1540-9538 0022-1007 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2010 |
| الوصف: | Classic Kaposi sarcoma (KS) is exceedingly rare in children from the Mediterranean Basin, despite the high prevalence of human herpesvirus-8 (HHV-8) infection in this region. We hypothesized that rare single-gene inborn errors of immunity to HHV-8 may underlie classic KS in childhood. We investigated a child with no other unusually severe infectious or tumoral phenotype who died from disseminated KS at two years of age. Whole-exome sequencing in the patient revealed a homozygous splice-site mutation in STIM1, the gene encoding stromal interaction molecule 1, which regulates store-operated Ca2+ entry. STIM1 mRNA splicing, protein production, and Ca2+ influx were completely abolished in EBV-transformed B cell lines from the patient, but were rescued by the expression of wild-type STIM1. Based on the previous discovery of STIM1 deficiency in a single family with a severe T cell immunodeficiency and the much higher risk of KS in individuals with acquired T cell deficiencies, we conclude that STIM1 T cell deficiency precipitated the development of lethal KS in this child upon infection with HHV-8. Our report provides the first evidence that isolated classic KS in childhood may result from single-gene defects and provides proof-of-principle that whole-exome sequencing in single patients can decipher the genetic basis of rare inborn errors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1084/jem.20101597 |
| الإتاحة: | https://doi.org/10.1084/jem.20101597Test https://rupress.org/jem/article-pdf/207/11/2307/1746502/jem_20101597.pdfTest |
| رقم الانضمام: | edsbas.8B0FE4B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1084/jem.20101597 |
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