title: Novel sequence variants and a high frequency of recurrent polymorphisms in BRCA1 gene in Sri Lankan breast cancer patients and at risk individuals.
abstract: BACKGROUND
  Breast Cancer is the most commonly diagnosed cancer among Sri Lankan women. Germline mutations in the susceptibility genes BRCA1 and BRCA2 in hereditary breast/ovarian cancer, though low in prevalence, are highly penetrant and show geographical variations. There have been only a few reports from Asia on mutations in BRCA1/2 genes and none from Sri Lanka.
  
  
  METHODS
  A total of 130 patients with (N = 66) and without (N = 64) a family history of breast cancer, 70 unaffected individuals with a family history of breast cancer and 40 control subjects were analysed for BRCA1 mutations. All but exon 11 were screened by single strand conformation analysis (SSCP) and heteroduplex analysis. PCR products which showed abnormal patterns in SSCP were sequenced. Exon 11 was directly sequenced.
  
  
  RESULTS
  Nineteen sequence variants were found in BRCA1 gene. Two novel deleterious frame-shift mutations; c.3086delT/exon11 (in one patient) and c.5404delG/exon21 (in one patient and two of her family members) were identified. A possibly pathogenic novel missense mutation (c.856T>G/exon 11) and three novel intronic variants (IVS7+36C>T, IVS7+41C>T, IVS7+49del15) were characterised. Ten previously reported common polymorphisms and three previously reported intronic variants were also observed.
  
  
  CONCLUSIONS
  After screening of 66 patients with family history and 64 sporadic breast cancer patients, 2 deleterious mutations (c.3086delT and c.5404delG) in two families were identified and two more possibly pathogenic mutations (c.856T>G and IVS17-2A>T) in two families were identified.
  
  
  METHODS
  BRCA1--Gene Bank: Accession # U14680 Version # 14680.1.
authors.affiliation: Institute of Biochemistry Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka. Wasanthi_e@yahoo.co.uk
authors.forename: Wasanthi
authors.initials: W
authors.lastname: De Silva
authors.forename: Eric H
authors.initials: EH
authors.lastname: Karunanayake
authors.forename: Kamani H
authors.initials: KH
authors.lastname: Tennekoon
authors.forename: Marie
authors.initials: M
authors.lastname: Allen
authors.forename: Indrani
authors.initials: I
authors.lastname: Amarasinghe
authors.forename: Preethika
authors.initials: P
authors.lastname: Angunawala
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Ziard
mesh_terms: D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D005843:Geography; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012008:Recurrence; D012306:Risk; D013188:Sri Lanka