title: Deletion of exons 1a-2 of BRCA1: a rather frequent pathogenic abnormality.
abstract: Women carrying a pathogenic mutation in either BRCA1 or BRCA2 have a major risk of developing breast and/or ovarian cancer. The majority of mutations in these genes are small point mutations. Since the development of multiplex ligation-dependent probe amplification, an increasing number of large genomic rearrangements have been detected. Here, we describe the characterization of pathogenic deletions of exons 1a-2 of BRCA1 in six families using loss of heterozygosity, array comparative genomic hybridization, and sequence analyses. Two families harbor a 37 kb deletion starting in intron 2 of psi BRCA1, encompassing NBR2, and exons 1a-2 of BRCA1, while the other four families have an 8 kb deletion with breakpoints in intron 2 of NBR2 and intron 2 of BRCA1. This observation, together with the previously described families with exon 1a-2 deletions of BRCA1, demonstrates that this type of deletions is relatively frequent in breast/ovarian cancer families.
authors.affiliation: Department of Clinical Genetics, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam, The Netherlands. a.vandenouweland@erasmusmc.nl
authors.forename: Ans M W
authors.initials: AM
authors.lastname: van den Ouweland
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
authors.forename: Lambert C J
authors.initials: LC
authors.lastname: Dorssers
authors.forename: Monique M
authors.initials: MM
authors.lastname: van Veghel-Plandsoen
authors.forename: Hennie T
authors.initials: HT
authors.lastname: Brüggenwirth
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Withagen-Hermans
authors.forename: Johanna Margriet
authors.initials: JM
authors.lastname: Collée
authors.forename: Simon A
authors.initials: SA
authors.lastname: Joosse
authors.forename: Joan N R
authors.initials: JN
authors.lastname: Terlouw-Kromosoeto
authors.forename: Petra M
authors.initials: PM
authors.lastname: Nederlof
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005190:Family; D005260:Female; D019398:Genes, BRCA1; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007438:Introns; D019656:Loss of Heterozygosity; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D009693:Nucleic Acid Hybridization; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D004273:DNA, Neoplasm; D005819:Genetic Markers