The purpose of this review is to summarize current evidence about the BRCA1/2 founder mutations diversity in European populations. For the current manuscript only the unequivocally deleterious mutations were considered, excluding as yet the unclassified variants that could not be clearly related with pathogenicity. For the consistency, the unequivocal term “founder” is used for those mutations where haplotype studies revealed shared polymorphic markers consistent with common ancestor, or when unrelated mutation carriers were repeatedly identified (at least 3 times). Some mutations previously described as founder mutations in one country, subsequently are found at a higher proportion in other countries/regions as true founders. These mutations in adjacent countries will likely reflect the gradient transition from the “epicenter” over the time due to historical co-existence of different populations in the same region. Mutations that do not segregate with the same alleles are referred as “recurrent”. They presumably occurred several times at unstable ‘mutational hot spots’ parts of the gene. The mutation nomenclature will be generally presented according to Human Genome Variation Society (HGVS) recommendations ( http://www.hgvs.org/rec.html ); only at the first mutation mention the older BIC database ( http://research.nhgri.nih.gov/bic/ ) nomenclature will be used between the parentheses, where possible. BRCA1 is numbered by GeneBank U14680 reference sequence; BRCA2 is numbered by GeneBank U43746 reference sequence.
For the mutations distribution in other geographic regions or more detailed prevalence, penetrance and contribution to unselected for family history cancer cases, readers are referred to other review sources [ 3 , 4 , 6 , 27 – 30 ].