dc.contributor.author |
Fliegauf, M |
en |
dc.contributor.author |
Bryant, VL |
en |
dc.contributor.author |
Frede, N |
en |
dc.contributor.author |
Slade, C |
en |
dc.contributor.author |
Woon, See-Tarn |
en |
dc.contributor.author |
Lehnert, Klaus |
en |
dc.contributor.author |
Winzer, S |
en |
dc.contributor.author |
Bulashevska, A |
en |
dc.contributor.author |
Scerri, T |
en |
dc.contributor.author |
Leung, Yee Fun |
en |
dc.contributor.author |
Jordan, A |
en |
dc.contributor.author |
Keller, B |
en |
dc.contributor.author |
de Vries, E |
en |
dc.contributor.author |
Cao, H |
en |
dc.contributor.author |
Yang, F |
en |
dc.contributor.author |
Schäffer, AA |
en |
dc.contributor.author |
Warnatz, K |
en |
dc.contributor.author |
Browett, Peter |
en |
dc.contributor.author |
Douglass, J |
en |
dc.contributor.author |
Ameratunga, RV |
en |
dc.contributor.author |
van der Meer, JW |
en |
dc.contributor.author |
Grimbacher, B |
en |
dc.date.accessioned |
2017-04-10T23:53:49Z |
en |
dc.date.issued |
2015-09-03 |
en |
dc.identifier.citation |
American Journal of Human Genetics 97(3):389-403 03 Sep 2015 |
en |
dc.identifier.issn |
0002-9297 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/32555 |
en |
dc.description.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 family with a heterozygous in-frame exon 9 skipping mutation (c.835+2T>G) and in a CVID-affected family from New Zealand with a heterozygous frameshift mutation (c.465dupA) in exon 7. Given that residual p105 and p50—translated from the non-mutated alleles—were normal, and altered p50 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-κB1 p50 haploinsufficiency. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.publisher |
Elsevier (Cell Press) |
en |
dc.relation.ispartofseries |
American Journal of Human Genetics |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Humans |
en |
dc.subject |
Common Variable Immunodeficiency |
en |
dc.subject |
DNA Primers |
en |
dc.subject |
Microscopy, Fluorescence |
en |
dc.subject |
Blotting, Western |
en |
dc.subject |
Sequence Analysis, DNA |
en |
dc.subject |
Base Sequence |
en |
dc.subject |
Molecular Sequence Data |
en |
dc.subject |
Australia |
en |
dc.subject |
Netherlands |
en |
dc.subject |
New Zealand |
en |
dc.subject |
NF-kappa B p50 Subunit |
en |
dc.subject |
Haploinsufficiency |
en |
dc.subject |
Exome |
en |
dc.title |
Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.ajhg.2015.07.008 |
en |
pubs.issue |
3 |
en |
pubs.begin-page |
389 |
en |
pubs.volume |
97 |
en |
dc.rights.holder |
Copyright: Elsevier (Cell Press) |
en |
dc.identifier.pmid |
26279205 |
en |
pubs.end-page |
403 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
495183 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Molecular Medicine |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1537-6605 |
en |
pubs.record-created-at-source-date |
2017-04-11 |
en |
pubs.dimensions-id |
26279205 |
en |