Journal article
Epistatic interactions between mutations of TACI (TNFRSF13B) and TCF3 result in a severe primary immunodeficiency disorder and systemic lupus erythematosus
R Ameratunga, W Koopmans, ST Woon, E Leung, K Lehnert, CA Slade, JC Tempany, A Enders, R Steele, P Browett, PD Hodgkin, VL Bryant
Clinical and Translational Immunology | WILEY | Published : 2017
DOI: 10.1038/CTI.2017.41
Abstract
Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies where monogenetic causes account for only a fraction of cases. On this evidence, CVID is potentially polygenic and epistatic although there are, as yet, no examples to support this hypothesis. We have identified a non-consanguineous family, who carry the C104R (c.310T4C) mutation of the Transmembrane Activator Calcium-modulator and cyclophilin ligand Interactor (TACI, TNFRSF13B) gene. Variants in TNFRSF13B/TACI are identified in up to 10% of CVID patients, and are associated with, but not solely causative of CVID. The proband is heterozygous for the TNFRSF13B/TACI C104R mutation and meets the Ameratun..
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Awarded by Australasian Society of Clinical Immunology and Allergy
Funding Acknowledgements
We are extremely grateful to this family for allowing us to undertake these studies for the benefit of others. We hope this discovery will benefit them and any future families with digenic disorders. We thank AMRF, A+ Trust, IDFNZ, ASCIA and the Australian National Health and Medical Research Council (NHMRC, Program Grant 1054925, Project Grant 1127198 and Independent Research Institutes Infrastructure Support Scheme Grant 361646) for grant support. We also received support from Bloody Long Way (BLW) the Victorian State Government Operational Infrastructure scheme and Walter and Eliza Hall Institute (WEHI) Innovation Grant. CAS is supported by NHMRC postgraduate scholarship 1075666. JCT is the recipient of an Australian Postgraduate Award. We thank Dr Kitty Croxson, ADHB and LabPlus management for ongoing support. We thank Danny Lim and Claire Tarring for technical support. Bioinformatic analysis was supported by the New Zealand eScience Infrastructure. All studies were approved by Auckland Hospital (3435), NZ Ministry of Health (MEC/06/10/134) and WEHI Human Research Ethics Committee (HREC 10/02).