Author/Authors :
ATAEI-KACHOUEI, Mojgan Dept. of Medical Genetics - Faculty of Medical Sciences - Tarbiat Modares University, Tehran, Iran , Javad NADAF, Javad Dept. of Human Genetics - McGill University, Montreal, Canada , AKBARI, Mohammad Taghi Dept. of Medical Genetics - Faculty of Medical Sciences - Tarbiat Modares University, Tehran, Iran , ATRI, Morteza Cancer Research Institute - Tehran University of Medical Sciences, Tehran, Iran , MAJEWSKI, Jacek McGill University and Genome Quebec Innovation Center, Montreal, Canada , RIAZALHOSSEINI, Yasser McGill University and Genome Quebec Innovation Center, Montreal, Canada , GARSHASBI, Masoud Dept. of Medical Genetics - Faculty of Medical Sciences - Tarbiat Modares University, Tehran, Iran
Abstract :
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.
Keywords :
BRCA2 , Familial breast cancer , rs80359352 , STK11 , Iran
