Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency - DG Cases

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.

From: 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.