Clinical observation of a patient with TMEM127 and EGLN1 gene variants, pheochromocytoma and pancreatic tumor

Abstract

Pheochromocytoma/paraganglioma is a neuroendocrine tumor of chromaffin and nonchromaffin cells of the autonomic nervous system, in most cases localized in the medullary layer of the adrenal gland. Its development is often associated with genetic predisposition. More than 30% of adult patients have genetically determined PCC/PG. In the last decade, many genes predisposing to the manifestation of PCC/PG have been found: RET, VHL, NF1, SDHB, SDHC, SDHD, SDHA, SDHAF2, TMEM127, MAH, KIF1BP, PHD2, EGLN1, FH, H-RAS, IDH, SLC25A11, MDH2. Mutation of the oncosuppressor genes TMEM127 and EGLN1, which regulate the level of factors induced by HIF hypoxia, is extremely rare in patients with PCC/PG, and has not been described at all in combination with pancreatic tumor. To date, data on the clinical manifestations of these gene mutations are limited. Accumulating clinical data on patients with identified genetic alterations is important for predicting the course of the disease, clarifying the malignant potential and stratifying the risk of developing comorbid pathology. We present the clinical case of a 62-year-old patient with PCC/PG and pancreatic tumor in whom a previously undescribed combination of TMEM127 c.99G > A (p.S33S) and EGLN1 c.515C > T (p.A172V) gene variants was found.