[CIS PIDD] [cis-pidd] NFkappaB patietns

Mon Jun 6 00:39:18 EDT 2016

Dear Bodo, of course I am interested in this! You already have material of several of my families, did you already check with them? I have new families besides the ones you already know. And do you also want to include ‘single’ patients in this effort? best wishes, Esther

> Op 4 jun. 2016, om 22:58 heeft CIS-PIDD <cis-pidd at lists.clinimmsoc.org> het volgende geschreven:
> 
> Dear all,
> In September 2015 we published that heterozygous mutation in NFkappaB1 can cause an antibody deficiency (CVID):
> http://www.ncbi.nlm.nih.gov/pubmed/26279205 <http://www.ncbi.nlm.nih.gov/pubmed/26279205>
> 
> Am J Hum Genet. <http://www.ncbi.nlm.nih.gov/pubmed/26279205#> 2015 Sep 3;97(3):389-403. Epub 2015 Aug 13.
> Fliegauf M <http://www.ncbi.nlm.nih.gov/pubmed/?term=Fliegauf%20M%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>1, Bryant VL <http://www.ncbi.nlm.nih.gov/pubmed/?term=Bryant%20VL%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>2, Frede N <http://www.ncbi.nlm.nih.gov/pubmed/?term=Frede%20N%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>1, Slade C <http://www.ncbi.nlm.nih.gov/pubmed/?term=Slade%20C%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>3, Woon ST <http://www.ncbi.nlm.nih.gov/pubmed/?term=Woon%20ST%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>4, Lehnert K <http://www.ncbi.nlm.nih.gov/pubmed/?term=Lehnert%20K%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>5, Winzer S <http://www.ncbi.nlm.nih.gov/pubmed/?term=Winzer%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>1, Bulashevska A <http://www.ncbi.nlm.nih.gov/pubmed/?term=Bulashevska%20A%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>1, Scerri T <http://www.ncbi.nlm.nih.gov/pubmed/?term=Scerri%20T%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>2, Leung E <http://www.ncbi.nlm.nih.gov/pubmed/?term=Leung%20E%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>6, Jordan A <http://www.ncbi.nlm.nih.gov/pubmed/?term=Jordan%20A%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>7, Keller B <http://www.ncbi.nlm.nih.gov/pubmed/?term=Keller%20B%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>1, de Vries E <http://www.ncbi.nlm.nih.gov/pubmed/?term=de%20Vries%20E%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>8, Cao H <http://www.ncbi.nlm.nih.gov/pubmed/?term=Cao%20H%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>9, Yang F <http://www.ncbi.nlm.nih.gov/pubmed/?term=Yang%20F%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>9, Schäffer AA <http://www.ncbi.nlm.nih.gov/pubmed/?term=Sch%C3%A4ffer%20AA%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>10, Warnatz K <http://www.ncbi.nlm.nih.gov/pubmed/?term=Warnatz%20K%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>1, Browett P <http://www.ncbi.nlm.nih.gov/pubmed/?term=Browett%20P%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>6, Douglass J <http://www.ncbi.nlm.nih.gov/pubmed/?term=Douglass%20J%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>11, Ameratunga RV <http://www.ncbi.nlm.nih.gov/pubmed/?term=Ameratunga%20RV%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>4, van der Meer JW <http://www.ncbi.nlm.nih.gov/pubmed/?term=van%20der%20Meer%20JW%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>12, Grimbacher B <http://www.ncbi.nlm.nih.gov/pubmed/?term=Grimbacher%20B%5BAuthor%5D&cauthor=true&cauthor_uid=26279205>13
> Haploinsufficiency of the NF-?B1 Subunit p50 in Common Variable Immunodeficiency.
> 
> Since, it became clear that mutations in NFkappaB 1 and 2 actually account for the majority of mutations in CVID:
> Using next generation sequencing, we identified 33 mutations in NFKB1 and NFKB2 in a cohort of 320 CVID patients. Ten mutations in NFKB1 are predicted to lead to expression of truncated, non-functional proteins which undergo rapid decay, thus causing p50 haploinsufficiency. Four mutations are predicted to cause constitutive nuclear localization of aberrant p50 proteins and a shortcut or a delay in canonical NF-kappaB signaling. Fourteen missense variants were identified, with yet unknown effects. In NFKB2 we identified four frame-shift mutations leading to expression of unprocessable p100 precursor, and functional p52 haploinsufficiency. A novel frame-shift mutation suggests constitutive nuclear localization of a mutant p52. The phenotypical spectrum ranged from clinically inapparent IgG subclass deficiency to severe forms of CVID with progressing pulmonary disease, inflammatory bowel disease, and rheumatoid joint disease. In summary, mutations in NFKB1 or NFKB2 are highly prevalent and could account for approximately 10% of monogenetic defects in CVID.
> 
> (This is actually part of an abstract submitted to ESID 2016 by the following set of authors: Manfred Fliegauf, Katrin Hübscher, Jessica Rojas, Natalie Frede, Klaus Warnatz, Christian Klemann, Robin Kobbe, Vassilios Lougaris, Alessandro Plebani, Oliver Bartsch, Roya Sherkat, Mikko Seppänen, Lennart Hammarstöm, Vanessa Bryant, Jo Douglass, Anna Shcherbina, Siobhan Burns, Rohan Ameratunga, Jos van der Meer, and Bodo Grimbacher)
> 
> 
> Therefore, we now think it is time to publish a large case series on patients with mutations in NFkappaB1 and 2:
> To this end, I suggest to collect all the information of  patients with mutations in NFkappaB1;
> and to share the work-load, Dr Karin Chen <karin.chen at hsc.utah.edu <mailto:karin.chen at hsc.utah.edu>> from the Department of Pediatrics at the University of Utah will collect the clinical data from all NFkappaB2 patients. 
> 
> If you are interested in a collaboration, please reply to this Email:
> bodo.grimbacher at uniklinik-freiburg.de <mailto:bodo.grimbacher at uniklinik-freiburg.de>
> 
> Best regards,
> Yours, Bodo
> 
> ****************************************
> Univ.-Prof. Dr. med. B. Grimbacher
>  
> Scientific-Director
> CCI-Center for Chronic Immunodeficiency
> UNIVERSITÄTSKLINIKUM FREIBURG
> Tel.: 0761 270-77731  Fax: -77744
> Breisacherstraße 115, 79106 Freiburg
> bodo.grimbacher at uniklinik-freiburg.de <mailto:bodo.grimbacher at uniklinik-freiburg.de> 
> www.uniklinik-freiburg.de/cci <http://www.uniklinik-freiburg.de/cci>
>  
> and 
>  
> Consultant Immunologist
> Institute of Immunity & Transplantation
> Dept of Immunology
> Royal Free Hospital
> UNIVERSITY COLLEGE LONDON
> Pond Street
> London NW3 2QG
> b.grimbacher at ucl.ac.uk <mailto:b.grimbacher at ucl.ac.uk>
> www.centreforimmunodeficiency.com <http://www.centreforimmunodeficiency.com/>
> 
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