Screening for germline mutations in XXXX susceptibility genes in high-risk families in Israel.

@entity1 @entity43 @entity8958 @entity0 @entity5344 @entity24717 @entity5345 @entity5 @entity2674 @entity4311 @entity6069 @entity1412 @entity4638 @entity9516
UNASSIGNED: We evaluated the clinical utility of screening for mutations in 34 @entity5344 susceptibility genes in high-risk families in Israel. @entity1 were recruited from 12, 2012 to 6, 2015 from 8 medical centers. All @entity1 had high @entity5344 risk based on personal and family history. Genotyping was performed with the InVitae    platform. The study was approved by the ethics committees of the participating centers; all @entity1 gave a written informed consent before entering the study. Overall, 282 individuals participated in the study: 149 (53  %) of Ashkenazi descent, 80 (28  %) Jewish non-Ashkenazi descent, 22 (8  %) of mixed Ashkenazi/non-Ashkenazi origin, 21 (7  %) were non-Jewish Caucasians, and the remaining @entity1 (n  =  10-3.5  %) were of Christian Arabs/Druze/unknown ethnicity. For @entity0 @entity1 (n  =  165), the median (range) age at diagnosis was 46 (22-90) years and for @entity43 (n  =  15) 54 (38-69) years. Overall, 30 cases (10.6  %) were found to carry a pathogenic actionable mutation in the tested genes: 10 @entity5345 (3 non-founder mutations), 9 @entity2674 (8 non-founder mutations), and one each in the @entity24717 and @entity9516 genes. Furthermore, actionable mutations were detected in 9 more cases in 4 additional genes ( @entity4311 , @entity8958 , @entity4638 , and @entity1412 ). No pathogenic mutations were detected in the other genotyped genes. In this high-risk population, 10.6  % harbored an actionable pathogenic mutation, including non-founder mutations in @entity6069 and in additional @entity5 susceptibility genes, suggesting that high-risk families should be genotyped and be assigned a genotype-based @entity5 risk.
