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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. (2016) In Clinical Genetics
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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publication status
epub
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keywords
BRCA, Breast cancer, Founder mutation, Hereditary, Large genomic rearrangements, Ovarian cancer
in
Clinical Genetics
publisher
Wiley-Blackwell
external identifiers
  • Scopus:84983540132
ISSN
0009-9163
DOI
10.1111/cge.12824
language
English
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yes
id
0d805ff8-7afc-42d6-a5f4-0cb36d5e25ef
date added to LUP
2016-09-16 10:00:22
date last changed
2017-02-05 04:52:59
@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},
  keyword      = {BRCA,Breast cancer,Founder mutation,Hereditary,Large genomic rearrangements,Ovarian cancer},
  language     = {eng},
  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},
  year         = {2016},
}