Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population
<p>Worldwide variation in the distribution of <i>BRCA</i> mutations is well recognised, and for the Moroccan population no comprehensive studies about <i>BRCA</i> mutation spectra or frequencies have been published. We therefore performed mutation analysis of the <i&...
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| Format: | Article |
| Language: | English |
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Ivyspring International Publisher
2013-01-01
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| Series: | International Journal of Medical Sciences |
| Online Access: | http://www.medsci.org/v10p0060.htm |
| _version_ | 1818158526117183488 |
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| author | Abdelilah Laraqui, Nancy Uhrhammer, Idriss Lahlou-Amine, Hicham EL Rhaffouli, Jamila El Baghdadi, Mohamed Dehayni, Rahali Driss Moussaoui, Mohamed Ichou, Yassir Sbitti, Abderrahman Al Bouzidi, Said Amzazi, Yves-Jean Bignon |
| author_facet | Abdelilah Laraqui, Nancy Uhrhammer, Idriss Lahlou-Amine, Hicham EL Rhaffouli, Jamila El Baghdadi, Mohamed Dehayni, Rahali Driss Moussaoui, Mohamed Ichou, Yassir Sbitti, Abderrahman Al Bouzidi, Said Amzazi, Yves-Jean Bignon |
| author_sort | Abdelilah Laraqui, Nancy Uhrhammer, Idriss Lahlou-Amine, Hicham EL Rhaffouli, Jamila El Baghdadi, Mohamed Dehayni, Rahali Driss Moussaoui, Mohamed Ichou, Yassir Sbitti, Abderrahman Al Bouzidi, Said Amzazi, Yves-Jean Bignon |
| collection | DOAJ |
| description | <p>Worldwide variation in the distribution of <i>BRCA</i> mutations is well recognised, and for the Moroccan population no comprehensive studies about <i>BRCA</i> mutation spectra or frequencies have been published. We therefore performed mutation analysis of the <i>BRCA1</i> gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for <i>BRCA</i> testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the <i>BRCA1 </i>gene. 31.6 % (6/19) of familial cases and 1 % (1/102) of early-onset sporadic (< 45 years) were found to be associated with <i>BRCA1</i> mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA), one missense mutation (c.5095C>T), and one nonsense mutation (c.4942A>T). The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in <i>BRCA1</i>, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55), but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of <i>BRCA2</i> in BC is also under study.</p> |
| first_indexed | 2024-12-11T15:31:29Z |
| format | Article |
| id | doaj.art-92fd0eabb0184321ba4f42d5a4310c1c |
| institution | Directory Open Access Journal |
| issn | 1449-1907 |
| language | English |
| last_indexed | 2024-12-11T15:31:29Z |
| publishDate | 2013-01-01 |
| publisher | Ivyspring International Publisher |
| record_format | Article |
| series | International Journal of Medical Sciences |
| spelling | doaj.art-92fd0eabb0184321ba4f42d5a4310c1c2022-12-22T01:00:03ZengIvyspring International PublisherInternational Journal of Medical Sciences1449-19072013-01-011016067Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan PopulationAbdelilah Laraqui, Nancy Uhrhammer, Idriss Lahlou-Amine, Hicham EL Rhaffouli, Jamila El Baghdadi, Mohamed Dehayni, Rahali Driss Moussaoui, Mohamed Ichou, Yassir Sbitti, Abderrahman Al Bouzidi, Said Amzazi, Yves-Jean Bignon<p>Worldwide variation in the distribution of <i>BRCA</i> mutations is well recognised, and for the Moroccan population no comprehensive studies about <i>BRCA</i> mutation spectra or frequencies have been published. We therefore performed mutation analysis of the <i>BRCA1</i> gene in 121 Moroccan women diagnosed with breast cancer. All cases completed epidemiology and family history questionnaires and provided a DNA sample for <i>BRCA</i> testing. Mutation analysis was performed by direct DNA sequencing of all coding exons and flanking intron sequences of the <i>BRCA1 </i>gene. 31.6 % (6/19) of familial cases and 1 % (1/102) of early-onset sporadic (< 45 years) were found to be associated with <i>BRCA1</i> mutations. The pathogenic mutations included two frame-shift mutations (c.798_799delTT, c.1016dupA), one missense mutation (c.5095C>T), and one nonsense mutation (c.4942A>T). The c.798_799delTT mutation was also observed in Algerian and Tunisian BC families, suggesting the first non-Jewish founder mutation to be described in Northern Africa. In addition, ten different unclassified variants were detected in <i>BRCA1</i>, none of which were predicted to affect splicing. Most unclassified variants were placed in Align-GVGD classes suggesting neutrality. c.5117G>C involves a highly conserved amino acid suggestive of interfering with function (Align-GVGD class C55), but has been observed in conjunction with a deleterious mutation in a Tunisian family. These findings reflect the genetic heterogeneity of the Moroccan population and are relevant to genetic counselling and clinical management. The role of <i>BRCA2</i> in BC is also under study.</p>http://www.medsci.org/v10p0060.htm |
| spellingShingle | Abdelilah Laraqui, Nancy Uhrhammer, Idriss Lahlou-Amine, Hicham EL Rhaffouli, Jamila El Baghdadi, Mohamed Dehayni, Rahali Driss Moussaoui, Mohamed Ichou, Yassir Sbitti, Abderrahman Al Bouzidi, Said Amzazi, Yves-Jean Bignon Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population International Journal of Medical Sciences |
| title | Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population |
| title_full | Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population |
| title_fullStr | Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population |
| title_full_unstemmed | Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population |
| title_short | Mutation Screening of the BRCA1 Gene in Early Onset and Familial Breast/Ovarian Cancer in Moroccan Population |
| title_sort | mutation screening of the brca1 gene in early onset and familial breast ovarian cancer in moroccan population |
| url | http://www.medsci.org/v10p0060.htm |
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