title: Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency.
abstract: Heterozygous mutations in the NLRP12 gene have been found in patients with systemic auto-inflammatory diseases. However, the NLRP12-associated periodic fever syndromes show a wide clinical spectrum, including patients without classical diagnostic symptoms. Here, we report on a 20-year-old female patient diagnosed with common variable immunodeficiency (CVID), who developed intestinal amyloidosis and carried novel compound heterozygous mutations in NLRP12, identified by whole exome and transcriptome sequencing. CVID is a primary immunodeficiency characterized by low serum immunoglobulins, recurrent bacterial infections and development of malignancy, but it also presents with a magnitude of autoimmune features. Because of the unspecific heterogeneous clinical features of the disease, a delay in diagnosis is common. Secondary, inflammatory (AA type) amyloidosis has infrequently been observed in CVID patients. Based on our case observation and a critical review of the literature, we suggest that NLRP12 mutations might account for a small fraction of CVID patients with severe auto-inflammatory complications.
authors: Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Stockholm, Sweden; Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany; ImmunoDeficiencyCenter Leipzig (IDCL), Hospital St. Georg gGmbH Leipzig, Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies Leipzig, Leipzig, Germany. Electronic address: Stephan.Borte@ki.se.
authors: Stephan
authors: S
authors: Borte
authors: Ondokuz Mayıs University, Medical Faculty, Department of Pediatric Allergy and Immunology, Samsun, Turkey.
authors: Mehmet Halil
authors: MH
authors: Celiksoy
authors: Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany.
authors: Volker
authors: V
authors: Menzel
authors: Ondokuz Mayıs University, Medical Faculty, Department of Pediatric Nephrology, Samsun, Turkey.
authors: Ozan
authors: O
authors: Ozkaya
authors: Ondokuz Mayıs University, Medical Faculty, Department of Pathology, Samsun, Turkey.
authors: Fatma Zeynep
authors: FZ
authors: Ozen
authors: Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany.
authors: Lennart
authors: L
authors: Hammarström
authors: Ondokuz Mayıs University, Medical Faculty, Department of Pediatric Allergy and Immunology, Samsun, Turkey.
authors: Alisan
authors: A
authors: Yildiran
mesh_terms: D000686:Amyloidosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007410:Intestinal Diseases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D012313:RNA / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C476731:NLRP12 protein, human; D012313:RNA
keywords: Amyloidosis; CVID; Cold-induced autoimmune disease; Common variable immunodeficiency; NLRP12; Periodic fever syndromes