title: Large BRCA1 gene deletions are found in 3% of German high-risk breast cancer families.
abstract: We have tested for large BRCA1 gene rearrangements in German high-risk breast and ovarian cancer families previously screened negative for point mutations by dHPLC and sequencing. Using the novel MLPA method, two deletions of exons 1A, 1B and 2 and exon 17, respectively, were detected in four out of 75 families investigated in Southern Germany. An identical exon 17 deletion with the same breakpoints and a deletion of exons 1A, 1B and 2 were found by fluorescent multiplex PCR in two out of 30 families investigated in Northern Germany. Combining both populations, genomic rearrangements were found in 6% of the mutation-negative families and 3% of all high-risk families and account for 8% of all BRCA1 mutations. Our data indicate that the exon 17 deletion may be a founder mutation in the German population. The prevalence of BRCA1 gene deletions or duplications in our patients is similar to previous reports from Germany and France. Genomic quantification by MLPA is a useful method for molecular diagnostics in high-risk breast cancer families.
authors.affiliation: Institute of Human Genetics, Ruprecht-Karls University Heidelberg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Hartmann
authors.forename: Anika L
authors.initials: AL
authors.lastname: John
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Klaes
authors.forename: Wera
authors.initials: W
authors.lastname: Hofmann
authors.forename: Rainer
authors.initials: R
authors.lastname: Bielen
authors.forename: Rolf
authors.initials: R
authors.lastname: Koehler
authors.forename: Bart
authors.initials: B
authors.lastname: Janssen
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D018703:Founder Effect; D017353:Gene Deletion; D020440:Gene Duplication; D005787:Gene Frequency; D015321:Gene Rearrangement; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D015336:Molecular Probe Techniques; D010051:Ovarian Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction