Immune deficiencies, infection, and systemic immune disordersPRKDC mutations associated with immunodeficiency, granuloma, and autoimmune regulator–dependent autoimmunity
Section snippets
Methods
Details of the materials and methods used in this study are provided in the Methods section in this article's Online Repository at www.jacionline.org.
Clinical features of 2 patients with combined immunodeficiency
This male patient 1 (Pt1) was born to a consanguineous couple of Turkish background (Fig 1, A). A younger nonidentical twin brother died in the first year of life with a diagnosis of aspiration pneumonia, chronic diarrhea, and failure to thrive. At birth, Pt1 was unremarkable with normal weight and occipitofrontal head circumference. He was given a diagnosis of persistent asthma in the first 2 years of life and experienced occasional ear infections. At the age of 6 years, he presented with
Discussion
Extending the phenotype of patients with PRKDC mutations, we report here the cases of 2 unrelated patients with manifestations of CID with immunodeficiency, granuloma, and autoimmunity caused by a homozygous p.Leu3062Arg mutation in PRKDC. Recurrent infections were documented in both cases, but their clinical history did not reveal opportunistic infections. Inflammatory manifestations were prominent in Pt1, who was initially given a diagnosis of ANA-positive oligoarticular juvenile idiopathic
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Supported by Hospices Civils de Lyon, Société Francaise de Rhumatologie, INSERM and ANR (ANR-14-CE14-0026-03) (to A.B.), as well as National Institutes of Health grant CA162804 (to D.J.C.), CPRIT RP110465 (to D.J.C.), and LYRIC grant INCa_4664 (to C.C.). T.W.'s laboratory is supported by European Research Council (ERC-Stg 281025), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1, ENS de Lyon. Y.J.C. acknowledges the European Research Council (GA 309449).
Disclosure of potential conflict of interest: This study was supported by Hospices Civils de Lyon and INSERM, as well as National Institutes of Health (NIH) grant CA162804; CPRIT RP110465. G. I. Rice's institution has received funding from the European Research Council (GA309449: Fellowship to Y.J.C.). J. E. Walter and his institution have received funding from the NIH and National Institute of Allergy and Infectious Diseases (NIAID) (5K08AI103035). L. D. Notarangelo is employed at Boston Children's Hospital and is on the Board of Scientific Counselors of the NIAID and NIH, has received or has grants pending from the NIH and the March of Dimes, and receives royalties from UpToDate. M. Butte's institution has received funding from the NIH (R01 GM110482). H. Reumaux has received compensation for travel and other meeting-related expenses from the European League Against Rheumatism (EULAR). P. Cochat has received compensation for supplying expert testimony from Novartis, as well as for travel and other meeting-related expenses from Raptor Pharmaceuticals. M. van der Burg's institution received funding from ZonMW Vidi grant 91712323. Y. J. Crow has received funding from the European Research Council (GA 309449: Fellowship to Y.J.C.) and from the European Union's Seventh Framework Programme (FP7/2007-2013). J.-P. De Villartay's institution has received grants from INCa (PLBIO11-151) and Ligue National contre le Cancer. T. Walzer's institution has received funding from the European Research Council (ERC), and has received support for travel for this study or other purposes from ERC and his laboratory is supported by Agence Nationale de la Recherche, the European Research Council (ERC-Stg 281025), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1, and ENS de Lyon. A. Belot's institution has received funding from the Institut national de la santé et de la recherche médicale, the French Society of Rheumatology, and Hospices Civils de Lyon; he has received compensation for delivering expert testimony from Pfizer, as well as compensation for travel and other meeting-related expenses from Novartis; and he has received or has grants pending from Advances in Neuroblastoma Research 2014. The rest of the authors declare that they have no other relevant conflicts of interest.