title: Uncommon clinical presentations of pheochromocytoma and paraganglioma in two different patients affected by two distinct novel VHL germline mutations.
abstract: BACKGROUND
  The von Hippel-Lindau (VHL) syndrome is an inherited multitumour disorder characterized by clinical heterogeneity and high penetrance. Pheochromocytoma (Pheo) is present in 10%-15% of cases and can be isolated or associated with other lesions such as haemangioblastomas, kidney cysts or cancer and pancreatic lesions. In VHL patients, Pheos generally secrete norepinephrine and are located in the adrenals. Extra-adrenal Pheos (paragangliomas, PGLs) are rare.
  
  
  OBJECTIVE
  While performing genetic testing in patients affected by apparently sporadic Pheos or PGLs, we found two novel different VHL germline mutations in two females who presented with two distinct very uncommon clinical pictures. One patient was studied for the presence of an adrenal incidentaloma and the other for the presence of a neck tumour.
  
  
  RESULTS
  Patients coding regions and exon-intron boundaries of RET (exons 10, 11, 13-15), VHL, SDHD, SDHB and SDHC genes were amplified and sequenced. We identified two novel VHL point mutations: a L198V missense mutation in a 32-year-old female affected by a right adrenal compound and mixed tumour constituted by an epinephrine secreting Pheo, a ganglioneuroma and an adrenocortical adenoma, and a T152I missense mutation in a 24-year-old female affected by a left carotid body tumour. No other lesions were found in the patients or in the VHL mutation positive relatives.
  
  
  CONCLUSIONS
  These cases enlarge the list of VHL mutations and add new insights in the clinical variability of VHL disease, thus confirming the importance of genetic testing in patients affected by apparently sporadic Pheos or PGLs.
authors.affiliation: Department of Clinical Physiopathology, Division of Endocrinology, University of Florence, Florence, Italy.
authors.forename: Tonino
authors.initials: T
authors.lastname: Ercolino
authors.forename: Lucia
authors.initials: L
authors.lastname: Becherini
authors.forename: Andrea
authors.initials: A
authors.lastname: Valeri
authors.forename: Michele
authors.initials: M
authors.lastname: Maiello
authors.forename: Maria Sole
authors.initials: MS
authors.lastname: Gaglianò
authors.forename: Gabriele
authors.initials: G
authors.lastname: Parenti
authors.forename: Matteo
authors.initials: M
authors.lastname: Ramazzotti
authors.forename: Elisa
authors.initials: E
authors.lastname: Piscitelli
authors.forename: Lisa
authors.initials: L
authors.lastname: Simi
authors.forename: Pamela
authors.initials: P
authors.lastname: Pinzani
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
authors.forename: Donatella
authors.initials: D
authors.lastname: Degl'Innocenti
authors.forename: Nico
authors.initials: N
authors.lastname: Console
authors.forename: Carlo
authors.initials: C
authors.lastname: Bergamini
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D003598:Cytoskeletal Proteins; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D018832:Molecular Chaperones; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018832:Molecular Chaperones; C108825:VBP1 protein, human