Simultaneous Occurrence of Germline Pathogenic Allele Variants of TMEM127 and TP53 in a Brazilian Family With Li-Fraumeni Syndrome

Abstract Background: We will describe a Brazilian family whose index case had pheochromocytoma and in the evaluation of the genetic panel by Next Generation Sequence (NGS), the germline pathogenic variants in the TMEM127 and TP53 genes were identified. Clinical Case: A 32-year-old female patient with a clinical picture of paroxysms and difficult to control arterial hypertension, with a personal history of stroke and acute myocardial infarction. She had a 6.5 cm tumor in the right adrenal and urine metanephrine levels of 5.5 mg / g creatinine (VR <1 mg / g creatinine) compatible with pheochromocytoma. She underwent laparoscopic right adrenalectomy. There was a reversal of arterial hypertension and paroxysms. 10 years after adrenalectomy, she was diagnosed with bilateral breast cancer, she underwent radical total mastectomy and 2 years ago there was a recurrence of breast cancer and currently undergoing chemotherapy. Germinative genetic panel carried out by NGS had identified pathogenic variants c.1010G> A, p. (Arg337His) in heterozygosity in the TP53 gene and c.117_120del p. (Ile41Argfs * 39) in heterozygosis in the TMEM127 gene. Her 28-year-old daughter diagnosed bilateral breast cancer and meningeoma in the central nervous system and she had the same pathogenic variants germlines. Thus far, there is no clinical, laboratory or radiological picture of pheochromocytoma. Her 11-year-old granddaughter has only the pathogenic allele variant c.117_120del p. (Ile41Argfs * 39) in heterozygosity in the TMEM127 gene and thus far she has no clinical, laboratory and radiological picture of pheochromocytoma. Conclusion: This is the first case report of the simultaneous occurrence of pathogenic germline variants in the TMEM127 and TP53 genes. Reference: 11) Toledo RA et al Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary pheocromocytomas and paragangliomas. Nature Reviews Endocrinology 13, 233-247 (2017).