TY - JOUR
TI - Haplotype analysis reveals that the recurrent BRCA1 deletion of exons 23 and 24 is a Greek founder mutation
AU - Apostolou, P.
AU - Pertesi, M.
AU - Aleporou-Marinou, V.
AU - Dimitrakakis, C.
AU - Papadimitriou, C.
AU - Razis, E.
AU - Christodoulou, C.
AU - Fountzilas, G.
AU - Yannoukakos, D.
AU - Konstantopoulou, I.
AU - Fostira, F.
JO - Application of Clinical Genetics
PY - 2017
VL - 91
TODO - 3
SP - 482-487
PB - Wiley-Blackwell Publishing Ltd
SN - null
TODO - 10.1111/cge.12824
TODO - BRCA1 protein;  genomic DNA;  BRCA1 protein;  BRCA1 protein, human;  BRCA2 protein;  BRCA2 protein, human, adult;  age determination;  aged;  Article;  breast cancer;  controlled study;  exon;  female;  founder effect;  gene deletion;  gene frequency;  gene locus;  genetic susceptibility;  germline mutation;  Greece;  haplotype;  human;  major clinical study;  microsatellite marker;  ovary cancer;  polymerase chain reaction;  priority journal;  Sanger sequencing;  breast tumor;  gene deletion;  genetic predisposition;  genetic screening;  genetics;  haplotype;  middle aged;  Ovarian Neoplasms;  pathology;  pedigree, Adult;  Aged;  BRCA1 Protein;  BRCA2 Protein;  Breast Neoplasms;  Female;  Founder Effect;  Genetic Predisposition to Disease;  Genetic Testing;  Germ-Line Mutation;  Greece;  Haplotypes;  Humans;  Middle Aged;  Ovarian Neoplasms;  Pedigree;  Sequence Deletion
TODO - 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. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
ER -