A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

Abstract

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

Keywords: Chinese; Fanconi anemia; compound heterozygous mutations; hereditary breast cancer.

Figure 1

(A) Electropherogram showing that deletion of exon 22 on BRCA1 c.5406+7A>G splicing. Deletion was detected by cDNA sequencing, (B) Gel electropherogram showing that deletion of 74bp by RT-PCR on BRCA1 c.5406+7A>G. Lane M: 50-bp DNA ladder marker; lane C: Normal human cDNA control; lane S: Proband’s cDNA. HtNM: Heteroduplexes of wild-type and mutant; HmW: Homoduplexes of wild-type; HmM: Homoduplexes of mutant.

Figure 2

Pedigree of proband’s family. : carrier of BRCA1: c.5406+7A>G; r.5333_5406del74; p.Asp1778Glyfs*27 mutations; : carrier of BRCA1: c.4065_4068delTCAA; p.Asn1355Lysfs*10.

Figure 3

(A,B) Pedigree of the 2 families in our Hereditary Breast Cancer Family Registry with BRCA1: c.5406+7A>G; r.5333_5406del74; p.Asp1778Glyfs*27 mutations. : carrier of BRCA1: c.5406+7A>G; r.5333_5406del74; p.Asp1778Glyfs*27 mutations.