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A comprehensive reference for BRCA1/2 genes pathogenic variants in Iran: published, unpublished and novel

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Abstract

BRCA1 and BRCA2 are two prominent genes that account for about 20–40% of inherited breast cancer. Mutations in these genes are often associated with clustering of especially early-onset cancers in the family. The spectrum of BRCA variants showed a significant difference between geographic regions and ethnicities. The frequency and spectrum of BRCA mutations in Iran, a country in southwest Asia, have not yet been thoroughly studied. Here, for the first time, all published and not published BRCA pathogenic variants are presented. Among 1040 high risk families (1258 cases) which were detected, 116 families were found to carry pathogenic variants in either BRCA1 or BRCA2. Altogether 89 distinct types of pathogenic variants have been detected in Iran, including 41 in BRCA1 and 48 in BRCA2. 16 out of 89 mutations had not been previously reported in Iran and are presented for the first time in this article, among which 4 mutations are novel worldwide. 20% of families had one of the seven most commonly observed mutations, including c.81-1G > C, c.66_67delAG, c.4609C>T, c.1568delT, c.1961delA, in BRCA1 and: c.3751_3752insA, c.8585dupT in BRCA2. Combining the data from published articles and our study which has not been published before, a comprehensive table is created as a reference for entire BRCA pathogenic variants and their frequencies in Iran.

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Acknowledgements

We would like to thank the patients and their families who participated in this study

Funding

This study was funded by Motamed Cancer Institute.

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Authors and Affiliations

  1. Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, No 146, South Gandhi Ave, Vanak Sq., P.O.BOX: 1517964311, Tehran, Iran

    Keivan Majidzadeh-A, Shiva Zarinfam, Nasrin Abdoli, Fatemeh Yadegari, Rezvan Esmaeili, Azin Teimourzadeh & Mohamad Zamani

  2. Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran

    Leila Farahmand

  3. Department of Medical Genetics, Tarbiat Modares University, Tehran, Iran

    Mahdieh Taghizadeh

  4. Department of Genetics and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran

    Mansoor Salehi

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  1. Keivan Majidzadeh-A
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Contributions

KM-A designed and coordinated research and wrote the manuscript. Also patient recruitment and all genetic counsellings of MCI were done by him. SZ performed the experiments, analyzed the data, and collected information from previous studies. NA performed the experiments and analyzed the data. FY wrote the manuscript and collected data from previous studies. RE, LF, AT, and MT have contributed to the interpretation of the data, and the revision of the manuscript. MS and MZ provided us with some of the unpublished data that were collected as part of this study. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Keivan Majidzadeh-A.

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The authors declare that there are no conflict of interests.

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This study with research ethics code IR.ACECR.IBCRC.REC.1397.018 has been approved by the Ethics Committee of MCI.

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The patients/participants provided their written informed consent to participate in this study.

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Majidzadeh-A, K., Zarinfam, S., Abdoli, N. et al. A comprehensive reference for BRCA1/2 genes pathogenic variants in Iran: published, unpublished and novel. Familial Cancer 21, 137–142 (2022). https://doi.org/10.1007/s10689-021-00242-4

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