title: Haplotype analysis reveals that the recurrent BRCA1 deletion of exons 23 and 24 is a Greek founder mutation.
abstract: A recurrent large genomic rearrangement (LGR) encompassing exons 23 and 24 of the BRCA1 gene has been identified in breast-ovarian cancer families of Greek origin. Its breakpoints have been determined as c.5406 + 664_*8273del11052 (RefSeq: NM_007294.3) and a diagnostic polymerase chain reaction (PCR) has been set up for rapid screening. In a series of 2,092 high-risk families completely screened for BRCA1 and BRCA2 germline mutations, we have found the deletion in 35 families (1.68%), representing 7.83% of the mutations identified in both genes and 10.3% of the total BRCA1 mutations. In order to characterize this deletion as a founder mutation, haplotype analysis was conducted in 60 carriers from 35 families, using three BRCA1 intragenic microsatellite markers and four markers surrounding the BRCA1 locus. Our results demonstrate a common shared core disease-associated haplotype of 2.89Mb. Our calculations estimate that the deletion has originated from a common ancestor 1450 years ago, which most probably inhabited the Asia Minor area. The particular (LGR) is the third mutation of such type that is proven to have a Greek founder effect in the Greek population, illustrating the necessity for LGRs testing in individuals of Greek descent.
authors.affiliation: Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece.|Department of Genetics & Biotechnology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Apostolou
authors.affiliation: Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece.|Division of Hematology and Transfusion Medicine, Faculty of Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Pertesi
authors.affiliation: Department of Genetics & Biotechnology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Aleporou-Marinou
authors.affiliation: Breast Unit of the 1st Department of Obstetrics and Gynecology, Athens University Medical School, Athens, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Dimitrakakis
authors.affiliation: Department of Clinical Therapeutics, "Alexandra" Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Papadimitriou
authors.affiliation: Third Medical Oncology Department, Hygeia Hospital, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Razis
authors.affiliation: Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Christodoulou
authors.affiliation: School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
authors.affiliation: Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Yannoukakos
authors.affiliation: Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Konstantopoulou
authors.affiliation: Molecular Diagnostics Laboratory, INRaSTES, National Center for Scientific Research "Demokritos", Athens, Greece.
authors.forename: F
authors.initials: F
authors.lastname: Fostira
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006115:Greece; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D017384:Sequence Deletion
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA; breast cancer; founder mutation; hereditary; large genomic rearrangements; ovarian cancer