title: Gain of Function Mutations of PIK3CD as a Cause of Primary Sclerosing Cholangitis.
abstract: Gain of function (GOF) mutation in the p110δ catalytic subunit of the phosphatidylinositol-3-OH kinase (PIK3CD) is the cause of a primary immunodeficiency (PID) characterized by recurrent sinopulmonary infections and lymphoproliferation. We describe a family of two adults and three children with GOF mutation in PIK3CD, all with recurrent sinopulmonary infections and varied infectious and non-infectious complications. The two adults have Primary Sclerosing Cholangitis (PSC) without evidence of Cryptosporidium parvum infection and have required liver transplantation. PSC is a novel phenotype of GOF mutation in PIK3CD.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.|Division of Allergy/Clinical Immunology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Heather N
authors.initials: HN
authors.lastname: Hartman
authors.affiliation: Immunology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Niemela
authors.affiliation: Children's Hospital of Wisconsin, Milwaukee, WI, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Hintermeyer
authors.affiliation: Primary Immunodeficiency Clinic, National Institutes of Health, 10 Center Dr, Clinical Center, 2C410F, Bethesda, MD, 20892, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Garofalo
authors.affiliation: Immunology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stoddard
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.|Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Verbsky
authors.affiliation: Immunology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA. srosenzweig@cc.nih.gov.|Primary Immunodeficiency Clinic, National Institutes of Health, 10 Center Dr, Clinical Center, 2C410F, Bethesda, MD, 20892, USA. srosenzweig@cc.nih.gov.
authors.forename: Sergio D
authors.initials: SD
authors.lastname: Rosenzweig
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA. jroutes@mcw.edu.|Division of Allergy/Clinical Immunology, Medical College of Wisconsin, Milwaukee, WI, USA. jroutes@mcw.edu.|MACC Fund Research Center, Medical College of Wisconsin, Room 5064, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA. jroutes@mcw.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Routes
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002648:Child; D015209:Cholangitis, Sclerosing / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; C486018:PIK3CD protein, human
keywords: PIK3CD; immunodeficiency; primary sclerosing cholangitis; recurrent infections