Doyle Meagan R, Johnston J Martin
a Mercer University School of Medicine , Savannah , Georgia , USA.
b School of Medicine , Renown Children's Hospital, University of Nevada, Reno , USA.
Pediatr Hematol Oncol. 2018 Apr;35(3):203-207. doi: 10.1080/08880018.2018.1502852. Epub 2018 Sep 21.
Li-Fraumeni syndrome is an autosomal dominant cancer syndrome characterized by pathogenic variants in the TP53 gene on chromosome 17. The most common cancers in Li-Fraumeni kindreds include sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma. We report a 9-month-old male who was diagnosed with an adrenocortical tumor and later found to harbor a novel TP53 c.559 G > C germline variant, resulting in p.Gly187Arg. Family history included early-onset breast cancer in his paternal grandmother and paternal great-grandfather, as well as colon cancer at age 31 in a paternal cousin. The same TP53 variant was later confirmed in his paternal grandmother. Based on this information, his father (age 28, obligate carrier for the variant) was referred for colonoscopic screening and found to have multiple adenomatous polyps. This previously undescribed variant lies at an exon/intron boundary and is predicted to decrease splice site efficiency with resulting altered splicing or exon skipping. Our patient's family history provides limited evidence that this variant is a cause of Li-Fraumeni syndrome.
李-弗劳梅尼综合征是一种常染色体显性癌症综合征，其特征为17号染色体上TP53基因存在致病性变异。李-弗劳梅尼家族中最常见的癌症包括肉瘤、乳腺癌、脑肿瘤和肾上腺皮质癌。我们报告了一名9个月大的男性，他被诊断患有肾上腺皮质肿瘤，后来发现携带一种新的TP53基因c.559 G > C种系变异，导致p.Gly187Arg。家族史包括其 paternal祖母和 paternal曾祖父患有早发性乳腺癌，以及一位 paternal堂兄在31岁时患结肠癌。后来在他的 paternal祖母中证实了相同的TP53变异。基于这些信息，他的父亲（28岁，该变异的 obligate携带者）被转诊进行结肠镜筛查，发现有多个腺瘤性息肉。这个以前未描述的变异位于外显子/内含子边界，预计会降低剪接位点效率，导致剪接改变或外显子跳跃。我们患者的家族史提供了有限的证据表明该变异是李-弗劳梅尼综合征的病因。 （注：paternal这个词在文中多次出现，但不太明确具体准确中文表述，这里保留英文供参考，可根据实际准确意思替换成合适中文，比如“父系的”等 ）
