Document Type: Research Articles
Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, Université de Tunis El Manar, Campus universitaire1060 El Manar I Tunis, Tunisia.
Salah Azaiez Institute of Carcinology of Tunis, Boulevard 09 Avril, 1006 Bab Saadoun, Tunisia.
Laboratoire Diagnostic Génétique et Moléculaire, Centre Jean-Perrin, 63011 Clermont-Ferrand Cedex 01, France.
The aim of this study is to investigate the involvement of consanguinity on BRCA1/2 mutation incidence in Southern
Mediterranean populations and to confirm their low penetrance by comparison of their recurrence in sporadic and familial
breast cancer in a context of ancient consanguinity practice. Our study comprises of two parts: First, a comparison of
the consanguinity rates of the South Mediterranean countries in a relationship with the frequency of BRCA1 deleterious
mutations in breast cancer families and the recurrence of these mutations. Second, we investigated 23patients with a
family history of breast cancer, 51 patients without a family history of breast cancer using next-generation sequencing
of BRCA2 and then confirmed by Sanger sequencing for the novel mutation. As results, we clearly show a strong
relationship between the frequency of BRCA1 deleterious mutations in breast cancer families and rate of consanguinity,
since they are significantly inversely correlated. Four deleterious mutations were found in BRCA2 gene including a
novel frame-shift mutationc.9382_9383dup in a patient with familial breast cancer and three other frame-shift mutations
c.6591_6592del, c.1310_1313del and c.7654dup in patients with sporadic breast cancer.These results are discussed
in a context of selective pressure of ancient consanguinity practice. In conclusion, the study of BRCA1/2 gene in
Southern Mediterranean countries revealed low penetrance recurrent mutations in sporadic and familial breast cancer.
These mutations have been selected in a context of ancient consanguinity practice along with protective genetic and