Haploinsufficiency of the NF-κB1 Subunit p50 in Common Variable Immunodeficiency.
Am J Hum Genet
; 97(3): 389-403, 2015 Sep 03.
Article
em En
| MEDLINE
| ID: mdl-26279205
ABSTRACT
Common variable immunodeficiency (CVID), characterized by recurrent infections, is the most prevalent symptomatic antibody deficiency. In â¼90% 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 p50translated from the non-mutated alleleswere normal, and altered p50 proteins were absent, we conclude that the CVID phenotype in these families is caused by NF-κB1 p50 haploinsufficiency.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunodeficiência de Variável Comum
/
Subunidade p50 de NF-kappa B
/
Haploinsuficiência
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Europa
/
Oceania
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article