title: A novel loss-of-function heterozygous BRCA2 c.8946_8947delAG mutation found in a Chinese woman with family history of breast cancer.
abstract: BACKGROUND
  Breast cancer is the most frequent female malignancy worldwide. Among them, some cases have hereditary susceptibility in two leading genes, BRCA1 and BRCA2. Heterozygous germ line mutations in them are related with increased risk of breast, ovarian and other cancer, following autosomal dominant inheritance mode.
  
  
  RESULTS
  For purpose of early finding, early diagnosis and early treatment, mutation detecting of BRCA1/2 genes was performed in unselected 300 breast or ovarian patients and unaffected women using next-generation sequencing and then confirmed by Sanger sequencing. A non-previously reported heterozygous mutation c.8946_8947delAG (p.D2983FfsX34) of BRCA2 gene was identified in an unaffected Chinese woman with family history of breast cancer (her breast cancer mother, also carrying this mutation). The BRCA2-truncated protein resulted from the frame shift mutation was found to lose two putative nuclear localization signals and a Rad51-binding motif in the extreme C-terminal region by bioinformatic prediction. And then in vitro experiments showed that nearly all the mutant protein was unable to translocate to the nucleus to perform DNA repair activity. This novel mutant BRCA2 protein is dysfunction.
  
  
  CONCLUSIONS
  We classify the mutation into disease causing and conclude that it is the risk factor for breast cancer in this family. So, conducting the same mutation test and providing genetic counseling for this family is practically meaningful and significant. Meanwhile, the identification of this new mutation enriches the Breast Cancer Information Core database, especially in China.
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Center Laboratory, Bao'an Maternal and Children Healthcare Hospital, Key Laboratory of Birth Defects Research, Shenzhen, China.|Birth Defects Prevention Research and Transformation Team, Shenzhen, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Shenzhen University, The Second People's Hospital, Shenzhen, China.|Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Jian
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Shenzhen University, The Second People's Hospital, Shenzhen, China.
authors.forename: Xianming
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Deyong
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xia
authors.affiliation: Center Laboratory, Bao'an Maternal and Children Healthcare Hospital, Key Laboratory of Birth Defects Research, Shenzhen, China. xionglk@sina.cn.|Birth Defects Prevention Research and Transformation Team, Shenzhen, China. xionglk@sina.cn.
authors.forename: Likuan
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, China. duanma@fudan.edu.cn.
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002681:China; D005260:Female; D024522:Genes, BRCA2; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree
keywords: BRCA2; Breast cancer; Frame shift; Mutation; NLS; RAD51