Identification of a founder BRCA2 mutation in Sardinian breast cancer families.
The population of Sardinia is characterized by a relatively low level of genetic heterogeneity: therefore 'founder mutations' can be expected to be found. We analysed 17 probands from families with high incidence of breast cancer or breast and ovarian cancer by sequencing the full-length coding regions of BRCA1 and BRCA2 genes. A novel BRCA2 frame-shift mutation, 3951del3insAT, which produces a protein truncated at codon 1258, was observed in six patients with BC from the same village. The mutation was not found in unaffected females (matched on basis of ethnicity and age) with no family history of cancer. Haplotype analysis strongly suggests that all affected persons had a common ancestor. The identification of this clinically significant founder mutation may facilitate screening/testing for inherited risk of breast cancer.
Monne
Maria
M
Centro di Diagnostica Biomolecolare e Citogenetica Emato-Oncologica, San Francesco Hospital, ASL3 via Mannironi 1, 08100 Nuoro, Italy. labematologia.nuoro@tiscali.it
Piras
Giovanna
G
Fancello
Patrizia
P
Santona
Maria Cristina
MC
Uras
Antonella
A
Landriscina
Gennaro
G
Mastio
Giuseppe
G
Gabbas
Attilio
A
D000328:Adult; D000368:Aged; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics; D005260:Female; D018703:Founder Effect; D016368:Frameshift Mutation; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016609:Neoplasms, Second Primary / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology / Q000235:genetics; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion
D024682:BRCA2 Protein