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Complexity in unclassified auto-inflammatory disease: a case report illustrating the potential for disease arising from the allelic burden of multiple variants Tucker, Lori B.; Lamot, Lovro; Niemietz, Iwona; Chung, Brian K.; Cabral, David A.; Houghton, Kristin; Petty, Ross E.; Morishita, Kimberly A.; Rice, Gillian I.; Turvey, Stuart E.; et al.

Abstract

Background: Despite recent advances in the diagnosis and understanding of many autoinflammatory diseases, there are still a great number of patients with phenotypes that do not fit any clinically- and/or genetically-defined disorders. Case presentation: We describe a fourteen-year-old boy who presented at two and a half years of age with recurrent febrile episodes. Over the course of the disease, the episodes increased in frequency and severity, with new signs and symptoms continuing to appear. Most importantly, these included skin changes, splenomegaly and transaminitis. Only partial control of the disease was achieved with anti-IL-1 therapy. Extensive investigation showed generalized inflammation without immune deficiency, with increased levels of serum amyloid A and several pro-inflammatory cytokines including interferon-γ, as well as an increased type I interferon score. Exome sequence analysis identified P369S and R408Q variants in the MEFV innate immunity regulator, pyrin (MEFV) gene and T260 M and T320 M variants in the NLR family pyrin domain containing 12 (NLRP12) gene. Conclusion: Patients with unclassified and/or unexplained autoinflammatory syndromes present diagnostic and therapeutic challenges and collectively form a substantial part of every cohort of patients with autoinflammatory diseases. Therefore, it is important to acquire their full genomic profile through whole exome and/or genome sequencing and present their cases to a broader audience, to facilitate characterization of similar patients. A critical mass of well-characterized cases will lead to improved diagnosis and informed treatment.

Item Metadata

Title
Complexity in unclassified auto-inflammatory disease: a case report illustrating the potential for disease arising from the allelic burden of multiple variants
Creator
Tucker, Lori B.; Lamot, Lovro; Niemietz, Iwona; Chung, Brian K.; Cabral, David A.; Houghton, Kristin; Petty, Ross E.; Morishita, Kimberly A.; Rice, Gillian I.; Turvey, Stuart E.; Gibson, William T.; Brown, Kelly L.
Contributor
Children's Hospital (Vancouver, B.C.); Children's Hospital (Vancouver, B.C.). Research Institute
Publisher
BioMed Central
Date Issued
2019-10-28
Description
Background: Despite recent advances in the diagnosis and understanding of many autoinflammatory diseases, there are still a great number of patients with phenotypes that do not fit any clinically- and/or genetically-defined disorders. Case presentation: We describe a fourteen-year-old boy who presented at two and a half years of age with recurrent febrile episodes. Over the course of the disease, the episodes increased in frequency and severity, with new signs and symptoms continuing to appear. Most importantly, these included skin changes, splenomegaly and transaminitis. Only partial control of the disease was achieved with anti-IL-1 therapy. Extensive investigation showed generalized inflammation without immune deficiency, with increased levels of serum amyloid A and several pro-inflammatory cytokines including interferon-γ, as well as an increased type I interferon score. Exome sequence analysis identified P369S and R408Q variants in the MEFV innate immunity regulator, pyrin (MEFV) gene and T260 M and T320 M variants in the NLR family pyrin domain containing 12 (NLRP12) gene. Conclusion: Patients with unclassified and/or unexplained autoinflammatory syndromes present diagnostic and therapeutic challenges and collectively form a substantial part of every cohort of patients with autoinflammatory diseases. Therefore, it is important to acquire their full genomic profile through whole exome and/or genome sequencing and present their cases to a broader audience, to facilitate characterization of similar patients. A critical mass of well-characterized cases will lead to improved diagnosis and informed treatment.
Subject
Autoinflammatory disease; Periodic fever syndrome; Macrophage activation syndrome; Type I interferon score; NLRP12; MEFV; Interleukin-1
Genre
Article
Type
Text
Language
eng
Date Available
2019-10-28
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0384871
URI
http://hdl.handle.net/2429/72092
Affiliation
Medicine, Faculty of; Science, Faculty of; Other UBC; Non UBC; Medical Genetics, Department of; Microbiology and Immunology, Department of; Pediatrics, Department of
Citation
Pediatric Rheumatology. 2019 Oct 28;17(1):70
Publisher DOI
10.1186/s12969-019-0374-x
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s).
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)