Evidence of a founder mutation of BRCA1 in a highly homogeneous population from southern Italy with breast/ovarian cancer

Hum Mutat. 2001 Aug;18(2):163-4. doi: 10.1002/humu.1167.

Abstract

Several genes have been involved in the pathogenesis of hereditary breast/ovarian cancer (BOC), but mutations in the BRCA1 gene are by far the most recurrent. In this study, we report the identification of a founder mutation in a geographically and historically homogeneous population from Calabria, a south Italian region. A screening performed on 24 patients from unrelated families highlighted the high prevalence of a 5083del19 alteration in the BRCA1 gene, which accounts for 33% of the overall gene mutations. The same mutation was also detected in 4 patients, all of Calabrian origin, referred to us by research centres from the north of Italy. Allelotype analysis, performed on probands and unaffected family members revealed the presence a common allele, therefore suggesting a founder effect due to a common ancestor. Our findings underscore the importance of ethnic background homogeneity in patients' selection and highlight the usefulness of founder mutations as a potential tool for optimisation of preclinical diagnosis in gene carriers and therapeutic approaches in affected individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Breast Neoplasms / genetics*
  • DNA Mutational Analysis
  • Ethnicity / genetics
  • Exons / genetics
  • Female
  • Founder Effect*
  • Genes, BRCA1*
  • Haplotypes / genetics
  • Humans
  • Introns / genetics
  • Italy / ethnology
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Mutation / genetics*
  • Ovarian Neoplasms / genetics*
  • Polymorphism, Single-Stranded Conformational