| Summary: | <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>
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