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High prevalence of the c.1227_1228dup (p.Glu410GlyfsX43) mutation in Tunisian families affected with MUTYH-associated-polyposis

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Abstract

Germline mutations in the base excision repair gene MUTYH have been associated with recessive inheritance of multiple colorectal adenomas. Screening of the MUTYH gene was carried on index cases of 10 unrelated Tunisian families and on available DNA samples from some members. Three germline mutations: c.536A > G (p.Y179C), c.1187 G > A (p.G396D) and c.1227_1228dup (p.Glu410GlyfsX43), were identified in the homozygous or compound heterozygous state in 8 out of 10 families. The c.1227_1228dup (p.Glu410GlyfsX43) mutation was the most frequent, since it was found in biallelic homozygous in 7 probands and 2 members of family F1 and in compound heterozygous associated with the c.536 A > G (p.Y179C) or c.1187 G > A (p.G396D) in family F2. Haplotype analysis revealed that the 8 families are unrelated. Moreover, in sporadic colorectal cancer, the c.1227_1228dup (p.Glu410GlyfsX43) mutation was identified in 13 % of patients compared to the p.G396D and p.Y179C found in 1.2 and 2.12 % respectively. Our data shows the high prevalence of the p.Glu410GlyfsX43 mutation in Tunisian families affected with MUTYH associated polyposis as well as in sporadic colorectal carcinoma.

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Acknowledgments

We are indebted to the patients and their family members who agreed to participate in this study and to the Ministry of High Education and Scientific Research for financial support. We thank M. Jaoua for DNA sequencing, the Department of Biology-ISBS for Experion facility, Pr S. Masmoudi for helpful discussion on genotyping and Pr A. Abdelmaksoud for editing the manuscript.

Conflict of interest

No competing financial interests exist.

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Authors and Affiliations

  1. Department of Cancer Genetics, Laboratory of Biomass Valorisation and Eukaryotic Protein Expression, Center of Biotechnology of Sfax, University of Sfax, BPK 1177, 3018, Sfax, Tunisia

    Rania Abdelmaksoud-Dammak, Imen Miladi-Abdennadher, Ali Gargouri & Raja Mokdad-Gargouri

  2. Department of Gastroenterology, Hedi Chaker Hospital, Sfax, Tunisia

    Ali Amouri & Nabil Tahri

  3. Department of Anatomopathology, Habib Bourguiba Hospital, Sfax, Tunisia

    Lobna Ayadi & Abdelmajid Khabir

  4. Department of Surgery, Habib Bourguiba Hospital, Sfax, Tunisia

    Foued Frikha

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  1. Rania Abdelmaksoud-Dammak
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  2. Imen Miladi-Abdennadher
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  3. Ali Amouri
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  4. Nabil Tahri
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  6. Abdelmajid Khabir
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  8. Ali Gargouri
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  9. Raja Mokdad-Gargouri
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Correspondence to Raja Mokdad-Gargouri.

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Abdelmaksoud-Dammak, R., Miladi-Abdennadher, I., Amouri, A. et al. High prevalence of the c.1227_1228dup (p.Glu410GlyfsX43) mutation in Tunisian families affected with MUTYH-associated-polyposis. Familial Cancer 11, 503–508 (2012). https://doi.org/10.1007/s10689-012-9543-5

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  • DOI: https://doi.org/10.1007/s10689-012-9543-5

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