Evidence of a founder mutation of BRCA1 in a highly homogeneous population from southern Italy with breast/ovarian cancer.
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.
Baudi
F
F
Dipartimento di Medicina Sperimentale e Clinica "G. Salvatore", Università degli Studi di Catanzaro "Magna Graecia", Italy.
Quaresima
B
B
Grandinetti
C
C
Cuda
G
G
Faniello
C
C
Tassone
P
P
Barbieri
V
V
Bisegna
R
R
Ricevuto
E
E
Conforti
S
S
Viel
A
A
Marchetti
P
P
Ficorella
C
C
Radice
P
P
Costanzo
F
F
Venuta
S
S
D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D007558:Italy / Q000208:ethnology; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational