DDX58 and Classic Singleton-Merten Syndrome

Carlos R Ferreira, Yanick J Crow, William A Gahl, Pamela J Gardner, Raphaela Goldbach-Mansky, Sun Hur, Adriana Almeida de Jesús, Michele Nehrebecky, Ji Woo Park, Tracy A Briggs

Research output: Contribution to journalArticlepeer-review


Singleton-Merten syndrome manifests as dental dysplasia, glaucoma, psoriasis, aortic calcification, and skeletal abnormalities including tendon rupture and arthropathy. Pathogenic variants in IFIH1 have previously been associated with the classic Singleton-Merten syndrome, while variants in DDX58 has been described in association with a milder phenotype, which is suggested to have a better prognosis. We studied a family with severe, "classic" Singleton-Merten syndrome.|We undertook clinical phenotyping, next-generation sequencing, and functional studies of type I interferon production in patient whole blood and assessed the type I interferon promoter activity in HEK293 cells transfected with wild-type or mutant DDX58 stimulated with Poly I:C.|We demonstrate a DDX58 autosomal dominant gain-of-function mutation, with constitutive upregulation of type I interferon.|DDX58 mutations may be associated with the classic features of Singleton-Merten syndrome including dental dysplasia, tendon rupture, and severe cardiac sequela.
Original languageEnglish
Pages (from-to)75-80
Number of pages6
JournalJournal of clinical immunology
Issue number1
Publication statusPublished - 15 Jan 2019


  • Interferonopathy
  • Singleton-Merten syndrome
  • retinoic acid-inducible gene I
  • type I interferon

Research Beacons, Institutes and Platforms

  • Lydia Becker Institute


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