Founder BRCA1/2 mutations in the Europe: The Netherlands (Holland)

Several founder mutations in BRCA1/2 have been identified in Holland [94], where significant regional and cultural differences exist. The BRCA1 c.2685_2686delAA (BIC: 2804delAA) founder mutation probably originated approximately 32 generations (∼200 years) ago, was also reported few times in Belgium and accounted for 24% of all BRCA1/2 mutations [92]. BRCA1 c.2193del5 (BIC: 2312del5), and c.1292dupT (BIC: 1411insT) mutations were also commonly found [92, 94].

In the south-west of Holland two founder mutations: 3.8-kb deletion of BRCA1 exon 13, also known as c.4186-1643_4357+2020del3835 (BIC: del exon 13del3835/IVS12-1643del3835), and BRCA2 c.5351dupA (BIC: 5579insA) were found in families from two different geographical areas, and were prevalent respectively in Catholic (West Braband clustering) and Protestant (South Beveland clustering) families, reflecting religious endogamy [95]. Together with another Dutch BRCA2 founder mutation c.6275_6276delTT (BIC: 6503delTT), c.5351dupA accounts for 62% of hereditary breast/ovarian families [94, 95].

Slightly outdated (as of year 2002) list of published and unpublished BRCA1/2 mutations in Netherlands and Belgium can be found at http://www.humgen.nl/lab-devilee/Lab/b1nlmuts.htm.

Large genomic rearrangements (LGRs) in BRCA1 gene are surprisingly common in Dutch population and more than 30% of the BRCA1 related cases of hereditary breast cancer are due to copy number changes of one or more exon in this gene. The majority of these (25%) are due to two frequently occurring founder mutations: already described 3.8-kb deletion of exon 13 or 510-bp deletion of exon 22 [96], which can be easily detected by multiplex-ligation dependent probe amplification (MLPA) method.

My full review article: Janavicius R. Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control

TBC