Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans
- Tuijnenburg, P.
- Lango Allen, H.
- Burns, S.O.
- Greene, D.
- Jansen, M.H.
- Staples, E.
- Stephens, J.
- Carss, K.J.
- Biasci, D.
- Baxendale, H.
- Thomas, M.
- Chandra, A.
- Kiani-Alikhan, S.
- Longhurst, H.J.
- Seneviratne, S.L.
- Oksenhendler, E.
- Simeoni, I.
- de Bree, G.J.
- Tool, A.T.J.
- van Leeuwen, E.M.M.
- Ebberink, E.H.T.M.
- Meijer, A.B.
- Tuna, S.
- Whitehorn, D.
- Brown, M.
- Turro, E.
- Thrasher, A.J.
- Smith, K.G.C.
- Thaventhiran, J.E.
- Kuijpers, T.W.
- Adhya, Z.
- Alachkar, H.
- Anantharachagan, A.
- Antrobus, R.
- Arumugakani, G.
- Bacchelli, C.
- Baxendale, H.
- Bethune, C.
- Bibi, S.
- Boardman, B.
- Booth, C.
- Browning, M.
- Brownlie, M.
- Burns, S.
- Chandra, A.
- Clifford, H.
- Cooper, N.
- Davies, S.
- Dempster, J.
- Devlin, L.
- Doffinger, R.
- Drewe, E.
- Edgar, D.
- Egner, W.
- El-Shanawany, T.
- Gaspar, B.
- Ghurye, R.
- Gilmour, K.
- Goddard, S.
- Gordins, P.
- Grigoriadou, S.
- Hackett, S.
- Hague, R.
- Harper, L.
- Hayman, G.
- Herwadkar, A.
- Hughes, S.
- Huissoon, A.
- Jolles, S.
- Jones, J.
- Kelleher, P.
- Klein, N.
- Kuijpers, T.
- Kumararatne, D.
- Laffan, J.
- Allen, H.L.
- Lear, S.
- Longhurst, H.
- Lorenzo, L.
- Maimaris, J.
- Manson, A.
- McDermott, E.
- Millar, H.
- Mistry, A.
- Morrisson, V.
- Murng, S.
- Nasir, I.
- Nejentsev, S.
DOIAbstract
Background: The genetic cause of primary immunodeficiency disease (PID) carries prognostic information. Objective: We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource–Rare Diseases cohort. Methods: In the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a novel Bayesian method identified nuclear factor κB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n = 390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by mean...
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