title: Clinical variability and expression of the NBN c.657del5 allele in Nijmegen Breakage Syndrome.
abstract: Patients affected by the autosomal recessive Nijmegen Breakage Syndrome (NBS [MIM 251260]) have possibly the highest risk for developing a malignancy of all the chromosomal instability syndromes. This reflects the profound disturbance to genomic integrity and cellular homeostasis that is caused by the mutation of the essential mammalian gene, NBN. Whilst null-mutation of Nbn is lethal in the mouse, NBS patients survive due to the fact that the common human founder mutation, found in over 90% of patients, is in fact hypomorphic and leads, by alternative translation, to varying amounts of a partially functional carboxy-terminal protein fragment, p70-nibrin. The expression level of p70-nibrin correlates with cancer incidence amongst patients. Using real-time PCR we have now found that the variation in p70-nibrin expression cannot be attributed to differences in mRNA quantity and that nonsense-mediated mRNA decay is not responsible for the observed variation. We discuss an alternative explanation for p70-nibrin expression variation.
authors.affiliation: Institut für Humangenetik, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lins
authors.forename: Ryong
authors.initials: R
authors.lastname: Kim
authors.forename: Lars
authors.initials: L
authors.lastname: Krüger
authors.forename: Krystyna H
authors.initials: KH
authors.lastname: Chrzanowska
authors.forename: Eva
authors.initials: E
authors.lastname: Seemanova
authors.forename: Martin
authors.initials: M
authors.lastname: Digweed
mesh_terms: D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D049932:Nijmegen Breakage Syndrome / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger