A novel p.Gly187Arg TP53 variant appears to result in Li-Fraumeni syndrome

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.