Familial adenomatous polyposis (FAP) is a rare genetic disorder caused mainly by monoallelic mutations of APC gene. The hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominantly inherited disease, which mostly predisposes to breast and ovarian cancers as a result of germline mutations in BRCA1 or BRCA2 genes. In a family, mutations in two cancer susceptibility genes are extremely rare. We studied a family with a case of a 46 years-old woman affected with FAP and ovarian cancer. The patient was affected with profuse FAP since the age of 18 years and a serous ovarian cancer was diagnosed at the age of 45 years. She reported other FAP cases and one case of breast cancer in maternal family. Initially, she was tested for FAP predisposition with mutational analysis of APC gene that revealed the presence of a frameshift mutation, c.3927_3931delAAAGA (p.Glu1309AspfsX4). The presence of ovarian cancer in the patient and of a breast cancer case in the maternal family, suggested an extended analysis to HBOC susceptibility genes that led to the detection of a frameshift mutation, c.3756_3759delGTCT (p.Ser1253Argfs), in BRCA1 gene. The genetic analysis was extended also to family members. The occurrence of the double mutation in APC and BRCA1 genes in the patient was responsible for the onset of FAP and ovarian cancer respectively.

The genetic counselling in hereditary cancer with a careful analysis of the pedigree allows identifying the gene to be analyzed. The development of multi-gene panels testing for cancer predisposition, with next generation sequencing (NGS), may reveal mutations in genes of high and moderate penetrance for cancer, although at a low frequency and allows diagnosing a possible double heterozygosity. This enables an adjusted treatment for the affected patient and is critical as it allows initiation of early risk-reducing measures for identified mutation carriers among family members.

家族性腺瘤性息肉病（FAP）是一种罕见的遗传疾病，主要由APC基因的单等位基因突变引起。遗传性乳腺癌和卵巢癌（HBOC）综合征是一种常染色体显性遗传疾病，由于BRCA1或BRCA2基因的种系突变，大多易患乳腺癌和卵巢癌。在一个家庭中，两个癌症易感基因的突变极为罕见。我们研究了一个患有FAP和卵巢癌的46岁妇女的家庭。自18岁起，该患者就受到FAP的严重影响，并在45岁时被诊断出浆液性卵巢癌。她报告了其他FAP病例和一个孕妇家庭中的乳腺癌病例。最初，她通过APC基因突变分析测试了FAP的易感性，该分析揭示了移码突变的存在。3927_3931delAAAGA（p.Glu1309AspfsX4）。患者中存在卵巢癌，母亲家庭中存在乳腺癌病例，这表明对HBOC易感性基因进行了扩展分析，从而导致检测到BRCA1基因中的移码突变c.3756_3759delGTCT（p.Ser1253Argfs）。遗传分析也扩展到了家庭成员。患者中APC和BRCA1基因双重突变的发生分别与FAP和卵巢癌的发生有关。

通过对血统书进行仔细的分析，进行遗传性癌症的遗传咨询可以确定要分析的基因。利用下一代测序（NGS）进行的癌症易感性多基因检测技术的开发，可能揭示出对癌症具有高和中度外显率的基因中的突变，尽管其频率较低，并且可以诊断可能的双重杂合性。这使得能够对受影响的患者进行调整的治疗，并且至关重要，因为它允许针对家庭成员中已识别出的突变携带者采取早期降低风险的措施。