Double heterozygosity of BRCA2 and STK11 in familial breast cancer detected by exome sequencing

Background: germ-line mutations of brca1 and brca2 genes are responsible for approximately 25-30% of domi-nantly inherited familial breast cancers; still a big part of genetic component is unknown. the aim of this study was to investigate genetic causes of familial breast cancer in a pedigree with recessive pattern of inheritance. methods: we applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer. sanger sequencing was applied for validation and segregation analysis of mutations. results: here,we describe a family with three affected sisters of early-onset invasive ductal carcinoma due to hetero-zygous frame shift mutation rs80359352 in brca2 gene as the first report in iranian patients in association with a novel missense snp of stk11 (p.s422g). these mutations are inherited from their normal father. conclusion: despite apparent recessive pattern of inheritance a dominant gene (here brca2) can be involved in pathogenesis of hereditary breast cancer which can be explained by incomplete penetrance of brca2 mutations. © 2015,iranian journal of public health. all rights reserved.