title: Identification of a novel in-frame deletion in BRCA2 and analysis of variants of BRCA1/2 in Italian patients affected with hereditary breast and ovarian cancer.
abstract: BACKGROUND
  An estimated 5 % – 10 % of all breast cancers are due to an inherited predisposition and, out of these, about 30 % are caused by germline mutations of the BRCA1 and BRCA2 genes. The prevalence of germline mutations in theBRCA1 and BRCA2 genes varies among ethnic groups. The aims of this study are to evaluate deleterious mutations and genomic rearrangements in BRCA1/2 genes and the CHEK21100delC mutation in a cohort of Italian women affected with hereditary breast and/or ovarian cancer. In addition we clarify the effect of the novel variants identified in BRCA2 gene bymRNA analysis and prediction software.
  
  
  METHODS
  We enrolled 103 consecutive Italian patients affected with hereditary breast and/or ovarian cancer, aged23 – 69 years.
  
  
  RESULTS
  We found BRCA1/2 mutations in 15/103 probands(14.6 % ). Among these, a BRCA2 gene mutation has not been described previously. In addition, we identified five novel BRCA2 variants (S1341, IVS1-59t > c, IVS11-74insA, IVS12 + 74c > g and I1167V). No genomic BRCA1/2re arrangements or CHEK2 1100delC mutation was found in our patients. The novel BRCA2 mutation NS1742del(p.N1742_S1743del) was an in-frame 6 bp deletion that results in loss of two amino acids.
  
  
  CONCLUSIONS
  In silico analysis conducted for S1341, IVS1-59t > c, IVS11-74insA and IVS12 + 74c > g of BRCA2 predicted the variants as neutral and benign, whereas the results for I1167V was inconclusive. mRNA analysis for the novel BRCA2 intronic variant IVS11-74insA and the already published BRCA1 variant C197 shows that they have no effect on the splicing. These results are in agreement with in silico analysis.
authors.affiliation: Dipartimento di Patologia Generale , Facoltà di Medicina e Chirurgia Seconda Università degli studi, Naples , Italy
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Vietri
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Molinari
authors.forename: Maria
authors.initials: M
authors.lastname: Laura De Paola
authors.forename: Flavia
authors.initials: F
authors.lastname: Cantile
authors.forename: Morena
authors.initials: M
authors.lastname: Fasano
authors.forename: Michele
authors.initials: M
authors.lastname: Cioffi
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D017353:Gene Deletion; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger