title: Double Heterozygosity of BRCA2 and STK11 in Familial Breast Cancer Detected by Exome Sequencing.
abstract: BACKGROUND
  Germ-line mutations of BRCA1 and BRCA2 genes are responsible for approximately 25-30% of dominantly 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 heterozygous 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dept. of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Ataei-Kachouei
authors.affiliation: Dept. of Human Genetics, McGill University, Montreal, Canada.
authors.forename: Javad
authors.initials: J
authors.lastname: Nadaf
authors.affiliation: Dept. of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Akbari
authors.affiliation: Cancer Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Atri
authors.affiliation: McGill University and Genome Quebec Innovation Center, Montreal, Canada.
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.affiliation: McGill University and Genome Quebec Innovation Center, Montreal, Canada.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Riazalhosseini
authors.affiliation: Dept. of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Garshasbi
keywords: BRCA2; Familial breast cancer; Iran; STK11; rs80359352