Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100

Lee, Cindy Eunhee, Fulcher, David A., Whittle, Belinda, Chand, Rochna, Fewings, Nicole, Field, Matthew, Andrews, Daniel, Goodnow, Christopher C., and Cook, Matthew C. (2014) Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood, 124 (19). pp. 2964-2972.

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Abstract

Most genetic defects that arrest B-cell development in the bone marrow present early in life with agammaglobulinemia, whereas incomplete antibody deficiency is usually associated with circulating B cells. We report 3 related individuals with a novel form of severe B-cell deficiency associated with partial persistence of serum immunoglobulin arising from a missense mutation in NFKB2. Significantly, this point mutation results in a D865G substitution and causes a failure of p100 phosphorylation that blocks processing to p52. Severe B-cell deficiency affects mature and transitional cells, mimicking the action of rituximab. This phenotype appears to be due to disruption of canonical and noncanonical nuclear factor κB pathways by the mutant p100 molecule. These findings could be informative for therapeutics as well as immunodeficiency.

Item ID: 43577
Item Type: Article (Research - C1)
ISSN: 1528-0020
Funders: National Health and Medical Research Council (NHMRC), Bev and Alan Harvey Bequest (BAHB)
Projects and Grants: NHMRC Project Grant 585464, NHMRC Project Grant 1049760, NHMRC Project Grant 1016953
Date Deposited: 07 Sep 2016 06:04
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060102 Bioinformatics @ 25%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060408 Genomics @ 25%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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