title: A Novel Heterozygous Mutation in theSTAT1SH2 Domain Causes Chronic Mucocutaneous Candidiasis, Atypically Diverse Infections, Autoimmunity, and Impaired Cytokine Regulation.
abstract: Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency characterized by persistent or recurrent skin and mucosal surface infections withCandidaspecies. Different gene mutations leading to CMC have been identified. These include various heterozygous gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) that are not only associated with infections but also with autoimmune manifestations. Recently, twoSTAT1GOF mutations involving the Src homology 2 (SH2) domain have been reported, while so far, over 50 mutations have been described mainly in the coiled coil and the DNA-binding domains. Here, we present two members of a Dutch family with a novelSTAT1mutation located in the SH2 domain. T lymphocytes of these patients revealed STAT1 hyperphosphorylation and higher expression of STAT1 target genes. The clinical picture of CMC in our patients could be explained by diminished production of interleukin (IL)-17 and IL-22, cytokines important in the protection against fungal infections.
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Division of Clinical Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Faculty of Medicine, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Kornvalee
authors.initials: K
authors.lastname: Meesilpavikkai
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Laboratory Medical Immunology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Dik
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Laboratory Medical Immunology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schrijver
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Laboratory Medical Immunology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: Nagtzaam
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Laboratory Medical Immunology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Angelique
authors.initials: A
authors.lastname: van Rijswijk
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Pediatrics, Division of Infectious Disease and Immunology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Gertjan J
authors.initials: GJ
authors.lastname: Driessen
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center , Rotterdam , Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Spek
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Division of Clinical Immunology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: P Martin
authors.initials: PM
authors.lastname: van Hagen
authors.affiliation: Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Division of Clinical Immunology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Virgil A S H
authors.initials: VA
authors.lastname: Dalm
keywords: Src homology 2 domain; chronic mucocutaneous candidiasis; gain-of-function mutation; heterozygous mutation; signal transducer and activator of transcription 1