dc.contributor.author | Lelarge, Virginie | |
dc.contributor.author | Palanduz, Ayşe | |
dc.contributor.author | Abhyankar, Avinash | |
dc.contributor.author | Plancoulaine, Sabine | |
dc.contributor.author | Telhan, Leyla | |
dc.contributor.author | Boisson, Bertrand | |
dc.contributor.author | Picard, Capucine | |
dc.contributor.author | Dewell, Scott | |
dc.contributor.author | Zhao, Connie | |
dc.contributor.author | Jouanguy, Emmanuelle | |
dc.contributor.author | Feske, Stefan | |
dc.contributor.author | Abel, Laurent | |
dc.contributor.author | Casanova, Jean-Laurent | |
dc.contributor.author | Byun, Minji | |
dc.date.accessioned | 2021-03-04T18:40:12Z | |
dc.date.available | 2021-03-04T18:40:12Z | |
dc.date.issued | 2010 | |
dc.identifier.citation | Byun M., Abhyankar A., Lelarge V., Plancoulaine S., Palanduz A., Telhan L., Boisson B., Picard C., Dewell S., Zhao C., et al., "Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma", JOURNAL OF EXPERIMENTAL MEDICINE, cilt.207, ss.2307-2312, 2010 | |
dc.identifier.issn | 0022-1007 | |
dc.identifier.other | vv_1032021 | |
dc.identifier.other | av_8be9a4d8-9eec-4f8e-8fa4-b95247404d50 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12627/94674 | |
dc.identifier.uri | https://doi.org/10.1084/jem.20101597 | |
dc.description.abstract | 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. | |
dc.language.iso | eng | |
dc.subject | Tıbbi Ekoloji ve Hidroklimatoloji | |
dc.subject | Yaşam Bilimleri | |
dc.subject | Temel Bilimler | |
dc.subject | Tıp | |
dc.subject | Sağlık Bilimleri | |
dc.subject | Dahili Tıp Bilimleri | |
dc.subject | Klinik Tıp (MED) | |
dc.subject | Klinik Tıp | |
dc.subject | TIP, ARAŞTIRMA VE DENEYSEL | |
dc.subject | Yaşam Bilimleri (LIFE) | |
dc.subject | İmmünoloji | |
dc.title | Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma | |
dc.type | Makale | |
dc.relation.journal | JOURNAL OF EXPERIMENTAL MEDICINE | |
dc.contributor.department | Rockefeller University , , | |
dc.identifier.volume | 207 | |
dc.identifier.issue | 11 | |
dc.identifier.startpage | 2307 | |
dc.identifier.endpage | 2312 | |
dc.contributor.firstauthorID | 26749 | |