Hereditary breast cancer in Middle Eastern and North African (MENA) populations: Identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population

Wijden Mahfoudh, Noureddine Bouaouina, Slim Ben Ahmed, Sallouha Gabbouj, Jingxuan Shan, Rebecca Mathew, Nancy Uhrhammer, Yves Jean Bignon, Wafa Troudi, Amel Ben Ammar Elgaaied, Elham Hassen, Lotfi Chouchane

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Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon-intron boundaries using direct sequencing. Six families were found to carry BRCA1 mutations with a prevalence of 37.5%. Four different deleterious mutations were detected. Three truncating mutations were previously described: c.798-799delTT (916 delTT), c.3331-3334delCAAG (3450 delCAAG), c.5266dupC (5382 insC) and one splice site mutation which seems to be specific to the Tunisian population: c.212 + 2insG (IVS5 + 2insG). We also identified 15 variants of unknown clinical significance. The c.798-799delTT mutation occurred at an 18% frequency and was shared by three apparently unrelated families. Analyzing five microsatellite markers in and flanking the BRCA1 locus showed a common haplotype associated with this mutation. This suggests that the c.798-799delTT mutation is a Tunisian founder mutation. Our findings indicate that the Tunisian population has a spectrum of prevalent BRCA1 mutations, some of which appear as recurrent and founding mutations.

Original languageEnglish
Pages (from-to)1037-1046
Number of pages10
JournalMolecular Biology Reports
Issue number2
Publication statusPublished - 1 Feb 2012



  • BRCA1 mutations
  • Founder effect
  • Hereditary breast cancer
  • Tunisians

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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