Germline BRCA gene mutations are reportedly associated with hereditary breast 
and ovarian cancers. Identification of BRCA mutations greatly improves the 
preventive strategies and management of breast cancer. Sanger sequencing has 
been the gold standard in identifying these mutations. However, 4-28% of 
inherited BRCA mutations may be due to large genomic rearrangements (LGRs), 
which could be missed by using Sanger sequencing alone. Our aim is to evaluate 
the pick-up rate of LGRs in our cohort. A total of 1,236 clinically high-risk 
patients with breast and/or ovarian cancers were recruited through The Hong Kong 
Hereditary Breast Cancer Family Registry from 2007 to 2014. Full gene sequencing 
(either Sanger or next generation sequencing) and multiplex ligation-dependent 
probe amplification (MLPA) were performed. We identified 120 deleterious BRCA 
mutations: 57 (4.61%) were in BRCA1 and 63 (5.10%) were in BRCA2. LGRs accounted 
for 6.67% (8 of 120) of all BRCA mutations, whereas 8.77 % (5 of 57) were BRCA1 
mutations and 4.76% (3 of 63) were BRCA2 mutations. Through this integrated 
approach, both small nucleotide variations and LGRs could be detected. We 
suggest that MLPA should be incorporated into the standard practice for genetic 
testing to avoid false-negative results, which would greatly affect the 
management of these high-risk families.