Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women.

ABSTRACT:

Background

Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood.

Methods

From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2.

Results

The majority of TH (45.2 %) involved the three common Jewish mutati

SUBMITTER: Rebbeck TR 

PROVIDER: S-EPMC5106833 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature