title: The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript.
abstract: In a BRCA1 screening in familial breast cancer carried out in different centres in Spain, France, and United Kingdom, a missense mutation 330A>G which results in a Arg to Gly change at codon 71 (R71G) was independently identified in 6 families, all of them with Spanish ancestors. This residue coincides with the -2 position of the exon 5 donor splice site. We further investigated the effect of this base substitution on the splicing of BRCA1 mRNA. The sequence analysis of the cDNA indicated that 22 bp of exon 5 were deleted, creating with the first bases of exon 6 a termination codon at position 64, which results in a truncated protein. The BRCA1 haplotype of the R71G carrier patients and Spanish controls was analysed by use of six microsatellites located within or near BRCA1. Our results are consistent with the possibility that these families shared a common ancestry with BRCA1 R71G being a founder mutation of Spanish origin.
authors.affiliation: Unidad de Medicina Molecular, INGO-SERGAS, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Vega
authors.forename: B
authors.initials: B
authors.lastname: Campos
authors.forename: B
authors.initials: B
authors.lastname: Bressac-De-Paillerets
authors.forename: P M
authors.initials: PM
authors.lastname: Bond
authors.forename: N
authors.initials: N
authors.lastname: Janin
authors.forename: F S
authors.initials: FS
authors.lastname: Douglas
authors.forename: M
authors.initials: M
authors.lastname: Domènech
authors.forename: M
authors.initials: M
authors.lastname: Baena
authors.forename: C
authors.initials: C
authors.lastname: Pericay
authors.forename: C
authors.initials: C
authors.lastname: Alonso
authors.forename: A
authors.initials: A
authors.lastname: Carracedo
authors.forename: M
authors.initials: M
authors.lastname: Baiget
authors.forename: O
authors.initials: O
authors.lastname: Diez
mesh_terms: D017668:Age of Onset; D017398:Alternative Splicing; D019313:BRCA1 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D005192:Family Health; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013030:Spain; D014158:Transcription, Genetic
chemical_list: D019313:BRCA1 Protein; D012333:RNA, Messenger