Gain of Function Mutations of PIK3CD as a Cause of Primary Sclerosing Cholangitis

Heather N Hartman; Julie Niemela; Mary K Hintermeyer; Mary Garofalo; Jennifer Stoddard; James W Verbsky; Sergio D Rosenzweig; John M Routes

doi:10.1007/s10875-014-0109-1

Gain of Function Mutations of PIK3CD as a Cause of Primary Sclerosing Cholangitis

J Clin Immunol. 2015 Jan;35(1):11-4. doi: 10.1007/s10875-014-0109-1. Epub 2014 Oct 29.

Authors

Heather N Hartman^{1

2}, Julie Niemela³, Mary K Hintermeyer⁴, Mary Garofalo⁵, Jennifer Stoddard³, James W Verbsky^{1

6}, Sergio D Rosenzweig^{7

8}, John M Routes^{9

10

11}

Affiliations

¹ Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
² Division of Allergy/Clinical Immunology, Medical College of Wisconsin, Milwaukee, WI, USA.
³ Immunology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
⁴ Children's Hospital of Wisconsin, Milwaukee, WI, USA.
⁵ Primary Immunodeficiency Clinic, National Institutes of Health, 10 Center Dr, Clinical Center, 2C410F, Bethesda, MD, 20892, USA.
⁶ Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI, USA.
⁷ Immunology Service, Clinical Center, National Institutes of Health, Bethesda, MD, USA. [email protected].
⁸ Primary Immunodeficiency Clinic, National Institutes of Health, 10 Center Dr, Clinical Center, 2C410F, Bethesda, MD, 20892, USA. [email protected].
⁹ Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA. [email protected].
¹⁰ Division of Allergy/Clinical Immunology, Medical College of Wisconsin, Milwaukee, WI, USA. [email protected].
¹¹ MACC Fund Research Center, Medical College of Wisconsin, Room 5064, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA. [email protected].

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.

Keywords: PIK3CD; immunodeficiency; primary sclerosing cholangitis; recurrent infections.

Publication types

Case Reports
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Amino Acid Substitution
Child
Cholangitis, Sclerosing / enzymology*
Cholangitis, Sclerosing / genetics*
Cholangitis, Sclerosing / immunology
Class I Phosphatidylinositol 3-Kinases / genetics*
Class I Phosphatidylinositol 3-Kinases / immunology
Class I Phosphatidylinositol 3-Kinases / metabolism
Female
Heterozygote
Humans
Immunologic Deficiency Syndromes / enzymology
Immunologic Deficiency Syndromes / genetics
Immunologic Deficiency Syndromes / immunology
Liver / pathology
Male
Mutation, Missense*
Pedigree

Substances

Class I Phosphatidylinositol 3-Kinases
PIK3CD protein, human

Grants and funding

Z99 CL999999/Intramural NIH HHS/United States