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Haplotype analysis reveals that the recurrent BRCA1 deletion of exons 23 and 24 is a Greek founder mutation

Apostolou, P. ; Pertesi, M. LU ; Aleporou-Marinou, V. ; Dimitrakakis, C. ; Papadimitriou, C. ; Razis, E. ; Christodoulou, C. ; Fountzilas, G. ; Yannoukakos, D. and Konstantopoulou, I. , et al. (2017) In Clinical Genetics 91(3). p.482-487
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... (More)

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 1450years 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BRCA, Breast cancer, Founder mutation, Hereditary, Large genomic rearrangements, Ovarian cancer
in
Clinical Genetics
volume
91
issue
3
pages
482 - 487
publisher
Wiley-Blackwell
external identifiers
  • pmid:27357818
  • wos:000395007600017
  • scopus:84983540132
ISSN
0009-9163
DOI
10.1111/cge.12824
language
English
LU publication?
yes
id
0d805ff8-7afc-42d6-a5f4-0cb36d5e25ef
date added to LUP
2016-09-16 10:00:22
date last changed
2025-01-12 11:19:57
@article{0d805ff8-7afc-42d6-a5f4-0cb36d5e25ef,
  abstract     = {{<p>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 1450years 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.</p>}},
  author       = {{Apostolou, P. and Pertesi, M. and Aleporou-Marinou, V. and Dimitrakakis, C. and Papadimitriou, C. and Razis, E. and Christodoulou, C. and Fountzilas, G. and Yannoukakos, D. and Konstantopoulou, I. and Fostira, F.}},
  issn         = {{0009-9163}},
  keywords     = {{BRCA; Breast cancer; Founder mutation; Hereditary; Large genomic rearrangements; Ovarian cancer}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{482--487}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Clinical Genetics}},
  title        = {{Haplotype analysis reveals that the recurrent BRCA1 deletion of exons 23 and 24 is a Greek founder mutation}},
  url          = {{http://dx.doi.org/10.1111/cge.12824}},
  doi          = {{10.1111/cge.12824}},
  volume       = {{91}},
  year         = {{2017}},
}