A novel nucleotide oligomerisation domain 2 mutation in a family with Blau syndrome: Phenotype and function

Lawrence Tc Ong; Ueli Nachbur; Dorota Rowczenio; John B Ziegler; Eddy Fischer; Ming Wei Lin

doi:10.1177/1753425917727063

A novel nucleotide oligomerisation domain 2 mutation in a family with Blau syndrome: Phenotype and function

Innate Immun. 2017 Oct;23(7):578-583. doi: 10.1177/1753425917727063. Epub 2017 Aug 24.

Authors

Lawrence Tc Ong^{1

2}, Ueli Nachbur^{3

4}, Dorota Rowczenio⁵, John B Ziegler^{6

7}, Eddy Fischer⁸, Ming Wei Lin^{2

9}

Affiliations

¹ 1 Centre for Immunology, 107640 Westmead Institute for Medical Research , University of Sydney, New South Wales, Australia.
² 2 Department of Clinical Immunology and Immunopathology, ICPMR, 8539 Westmead Hospital , New South Wales, Australia.
³ 3 5388 Walter and Eliza Hall Institute , Parkville, Victoria, Australia.
⁴ 4 Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia.
⁵ 5 170705 National Amyloidosis Centre , Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, UCL, London, UK.
⁶ 6 Sydney Children's Hospital, Randwick, New South Wales, Australia.
⁷ 7 School of Women's and Children's Health, UNSW Australia, Sydney, New South Wales, Australia.
⁸ 8 6488 Nepean Hospital , Kingswood, New South Wales, Australia.
⁹ 9 Discipline of Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.

PMID: 28836875
DOI: 10.1177/1753425917727063

Abstract

Mutations in the nucleotide binding domain of the PRR, NOD2, are associated with the autoinflammatory diseases Blau syndrome and early-onset sarcoidosis. Current theories suggest that constitutive activation of the NOD2 pathway may be responsible for pathogenesis of these diseases. Here, we report the phenotype of a kindred with Blau syndrome caused by a novel NOD2 mutation (p.E383D). Signaling protein and cytokine expression were examined, and the results of these experiments challenge current theories of constitutive NOD2 activation in the pathophysiology of Blau syndrome.

Keywords: Autoinflammation; Blau syndrome; NOD2; early onset sarcoidosis; inflammasome.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Arthritis / diagnosis
Arthritis / genetics*
Autoimmunity / genetics
Child, Preschool
Cytokines / genetics
Cytokines / metabolism
Female
Genotype
Humans
Infant
Inflammasomes / metabolism*
Male
Middle Aged
Mutation / genetics*
Nod2 Signaling Adaptor Protein / genetics*
Nod2 Signaling Adaptor Protein / metabolism
Pedigree
Phenotype
Sarcoidosis / diagnosis
Sarcoidosis / genetics*
Signal Transduction
Synovitis / diagnosis
Synovitis / genetics*
Uveitis / diagnosis
Uveitis / genetics*
Young Adult

Substances

Cytokines
Inflammasomes
NOD2 protein, human
Nod2 Signaling Adaptor Protein

Supplementary concepts

Blau syndrome