Journal article
Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency
M Fliegauf, V L. Bryant, N Frede, C Slade, ST Woon, K Lehnert, S Winzer, A Bulashevska, T Scerri, E Leung, A Jordan, B Keller, E De Vries, H Cao, F Yang, AA Schäffer, K Warnatz, P Browett, J Douglass, RV Ameratunga Show all
American Journal of Human Genetics | Published : 2015
Abstract
Common variable immunodeficiency (CVID), characterized by recurrent infections, is the most prevalent symptomatic antibody deficiency. In ∼90% of CVID-affected individuals, no genetic cause of the disease has been identified. In a Dutch-Australian CVID-affected family, we identified a NFKB1 heterozygous splice-donor-site mutation (c.730+4A>G), causing in-frame skipping of exon 8. NFKB1 encodes the transcription-factor precursor p105, which is processed to p50 (canonical NF-κB pathway). The altered protein bearing an internal deletion (p.Asp191-Lys244delinsGlu; p105ΔEx8) is degraded, but is not processed to p50ΔEx8. Altered NF-κB1 proteins were also undetectable in a German CVID-affected fami..
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Awarded by National Institutes of Health
Funding Acknowledgements
We are deeply grateful to all the affected individuals and their families who participated in this study. We thank Mary Buchta, Franziska Nussbaumer, Pay la Mrovecova, Katrin Hubscher, Tobias Kratina, and Isabella Kong for their excellent technical assistance. We thank Marcel van Deuren for sharing clinical data on the Dutch family. This study was supported by the German Federal Ministry of Education and Research (01EO1303), E:med SysINFLAME Collaborative Project 1 (01ZX1306), the Australian National Health and Medical Research Council (1054925) and the Auckland Medical Research Foundation, the Auckland District Health Board Charitable Trust, and the New Zealand eScience Infrastructure. This work was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. C.S. was supported by National Health and Medical Research Council postgraduate scholarship 1075666.