{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:27:24Z","timestamp":1791289644193,"version":"4.3.0"},"reference-count":35,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,10,25]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1084\/jem.20101597","type":"journal-article","created":{"date-parts":[[2010,9,28]],"date-time":"2010-09-28T04:24:38Z","timestamp":1285647878000},"page":"2307-2312","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":282,"title":["Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma"],"prefix":"10.1084","volume":"207","author":[{"given":"Minji","family":"Byun","sequence":"first","affiliation":[{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 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