title: Familial pheochromocytoma and renal cell carcinoma syndrome: TMEM127 as a novel candidate gene for the association.
abstract: Germline mutations in Von Hippel-Lindau (VHL), succinate dehydrogenase subunit B (SDHB), SDHC, and SDHD have been detected in individuals with synchronous or metachronous pheochromocytoma/paraganglioma (PHEO/PGL) and renal cell carcinoma (RCC). Most recently, FH and TMEM127 germline mutations, which are known to cause familial PHEO/PGL, have also been identified in familial RCC. We report the first case of an individual with both a PHEO and a multilocular clear cell RCC driven by a novel germline mutation in the TMEM127 gene. Morphologically, both the PHEOs and multilocular RCC were indistinguishable from those associated with VHL disease. However, at the biochemical level, the predominant adrenergic catecholamine profile distinguishes this presentation from SDH- and VHL-related PHEOs. This case justifies the prioritization of genetic testing for germline TMEM127 in individuals with RCC and PHEO with a predominantly adrenergic phenotype.
authors: Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors: Karen Gomez
authors: KG
authors: Hernandez
authors: Shereen
authors: S
authors: Ezzat
authors: Chantal F
authors: CF
authors: Morel
authors: Carol
authors: C
authors: Swallow
authors: Mirek
authors: M
authors: Otremba
authors: Brendan C
authors: BC
authors: Dickson
authors: Sylvia L
authors: SL
authors: Asa
authors: Ozgur
authors: O
authors: Mete
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D013577:Syndrome; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C548370:TMEM127 protein, human