The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript

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. Hum Mutat 17:520–521, 2001. © 2001 Wiley‐Liss, Inc.

[1]  Anne M. Bowcock,et al.  Identification of a RING protein that can interact in vivo with the BRCA1 gene product , 1996, Nature Genetics.

[2]  E. Lyon,et al.  Implications of a novel cryptic splice site in the BRCA1 gene. , 1998, American journal of medical genetics.

[3]  H. Mefford,et al.  Evidence for a BRCA1 founder mutation in families of West African ancestry. , 1999, American journal of human genetics.

[4]  Jaana M. Hartikainen,et al.  Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland , 2000, European Journal of Human Genetics.

[5]  M. King,et al.  Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study. , 1998, American journal of human genetics.

[6]  H. Ozçelik,et al.  Mutation in the coding region of the BRCA1 gene leads to aberrant splicing of the transcript , 1999, Human mutation.

[7]  Ethnic differences in cancer risk resulting from genetic variation , 1999, Cancer.

[8]  K. Claes,et al.  Mutation Analysis of the BRCA1 and BRCA2 Genes in the Belgian Patient Population and Identification of a Belgian Founder Mutation BRCA1 IVS5+3A>G , 2002, Disease markers.

[9]  H. Breiteneder,et al.  New Austrian mutation in BRCA1 gene detected in three unrelated HBOC families , 1996, The Lancet.

[10]  B. Ward,et al.  BRCA1 IVS16+6T-->C is a deleterious mutation that creates an aberrant transcript by activating a cryptic splice donor site. , 1999, American journal of medical genetics.

[11]  D. Easton,et al.  Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. , 1995, American journal of human genetics.

[12]  Alfred A. Boyd,et al.  Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2 , 1996, Nature Genetics.

[13]  C. Alonso,et al.  BRCA1 mutation analysis in 83 Spanish breast and breast/ovarian cancer families , 1999, International journal of cancer.

[14]  A. Jonasdottir,et al.  Identification of a novel splice‐site mutation of the BRCA1 gene in two breast cancer families: Screening reveals low frequency in Icelandic breast cancer patients , 1998, Human mutation.

[15]  Chun-Fang Xu,et al.  Mutations and alternative splicing of the BRCA1 gene in UK breast/ovarian cancer families , 1997, Genes, chromosomes & cancer.

[16]  D. Clayton,et al.  Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype–phenotype correlation , 1995, Nature Genetics.