PDF(Pubmed)
Abstract：
Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline pathogenic variants in the tumor protein p53 (TP53) gene and elevated risk of a broad range of early-onset malignancies. Patients with LFS are at risk of a second and third primary tumor. A 15-month-old girl consulted for clitoromegaly and pubic hair. Adrenal ultrasound detected a large left adrenal tumor. Left total adrenalectomy confirmed adrenocortical carcinoma. Family history revealed multiple highly malignant neoplasms at an early age across five generations, and a genetic dominant trait seemed probable. Whole-genome sequencing was performed. Multiple members of the family were found positive for a novel likely pathogenic variant (c. 892delGinsTTT, p. Glu298PhefsX48, NM_000546.6) in the TP53 gene, causing the loss of normal protein function through non-sense-mediated mRNA decay. According to the PSV1 supporting criteria and the Auto PVS1 online tool this frameshift variant: hg19/17-7577045-TC-TAAA:NM_000546.6 has a very strong, definitive clinical validity for LFS with autosomal dominant inheritance. Proper guidance resulted in timely diagnosis of a second tumor (primary osteosarcoma) in the index case and in the early detection of breast and cervical cancer in her young mother. Patients with cancer predisposition syndromes like LFS require close multidisciplinary cancer surveillance and appropriate referral to expert centers.
摘要：
Li-Fraumeni综合征（LFS）是一种常染色体显性遗传性癌症综合征，与肿瘤蛋白p53（TP53）基因的种系致病变异有关，并增加了多种早发性恶性肿瘤的风险。LFS患者有第二和第三原发肿瘤的风险。一个15个月大的女孩咨询阴蒂肿大和阴毛。肾上腺超声检测到一个大的左肾上腺肿瘤。左全肾上腺切除术证实肾上腺皮质癌。家族史显示，在五代人的早期，多发性高度恶性肿瘤，遗传显性特征似乎很可能。进行全基因组测序。发现该家族的多个成员对一种新的可能的致病变体呈阳性（c。892delGinsTTT,p.TP53基因中的Glu298PhefsX48，NM_000546.6），通过无义介导的mRNA衰变导致正常蛋白质功能的丧失。根据PSV1支持标准和AutoPVS1在线工具，此移码变体：hg19/17-7577045-TC-TAAA：NM_000546.6具有非常强大的，具有常染色体显性遗传的LFS的最终临床有效性。正确的指导可及时诊断出索引病例中的第二个肿瘤（原发性骨肉瘤），并在年轻母亲中早期发现乳腺癌和宫颈癌。患有LFS等癌症易感性综合征的患者需要密切的多学科癌症监测并适当转诊到专家中心。
