A comprehensive reference for BRCA1/2 genes pathogenic variants in Iran: published, unpublished and novel

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• BRCA1 and BRCA2 gene mutations are significant contributors to hereditary breast cancer, accounting for 20-40% of cases.
• These mutations are linked to familial early-onset cancers, with variations differing across ethnicities and regions.
• The spectrum of BRCA mutations in Iran remains understudied.

Purpose of the Study:

• To comprehensively document all published and unpublished BRCA1 and BRCA2 pathogenic variants in Iran.
• To establish a reference for BRCA mutation frequencies and spectrum within the Iranian population.
• To identify novel BRCA mutations and those previously unreported in Iran.

Main Methods:

• Analysis of 1040 high-risk families (1258 cases) for BRCA1 and BRCA2 pathogenic variants.
• Compilation of data from published literature and unpublished findings.
• Identification and characterization of distinct pathogenic variants, including novel mutations.

Main Results:

• 116 out of 1040 families carried pathogenic variants in BRCA1 or BRCA2.
• A total of 89 distinct pathogenic variants were identified: 41 in BRCA1 and 48 in BRCA2.
• 16 variants were new to Iran, and 4 were novel worldwide. Seven common mutations accounted for 20% of cases.

Conclusions:

• This study provides the first comprehensive catalog of BRCA pathogenic variants in Iran.
• The findings highlight the genetic diversity of BRCA mutations in the region and identify key variants for screening.
• A combined dataset offers a valuable reference for future research and clinical management of hereditary breast cancer in Iran.