m>BRCA1m> and
m>BRCA2m> genes fro
m 167 candidates (145 fa
milies) were scanned for
mutations. We identified 14 pathogenic point
mutations in 17 candidates, 9 in
m>BRCA1m> and 5 in
m>BRCA2m>. Of those, 11 have been previously described and 3 were novel (c.5335C > T in
m>BRCA1m> and c.4139_4140dupTT and c.8175G > A in
m>BRCA2m>). No large deletions or duplications involving
m>BRCA1m> and
m>BRCA2m> genes were identified. No founder
mutations were detected for the Croatian population. Croatia shares
most of the
mutations with neighboring Slovenia and also with Ger
many, Austria and Poland.
Two common sequence variants in m>BRCA1m>, c.2077G > A and c.4956G > A, were found more frequently in mutation carriers compared to healthy controls. No difference in m>BRCA2m> variants was detected between the groups.
Haplotype inference showed no difference in haplotype distributions between deleterious mutation carriers and non-carriers in neither m>BRCA1m> nor m>BRCA2m>. In silico analyses identified one m>BRCA1m> sequence variant (c.4039A > G) and two m>BRCA2m> variants (c.5986G > A and c.6884G > C) as harmful with high probability, and inconclusive results were obtained for our novel m>BRCA2m> variant c.3864_3866delTAA.
Combination of QMPSF and HRMA methods provides high detection rate and complete coverage of m>BRCA1/2m> genes. Benefit of m>BRCA1/2m> mutation testing is clear, since we detected mutations in young unaffected women, who will be closely monitored for breast and ovarian cancer.