title: NF1 truncating mutations associated to aggressive clinical phenotype with elephantiasis neuromatosa and solid malignancies.
abstract: OBJECTIVE
  Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis.
  
  
  METHODS
  Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer.
  
  
  RESULTS
  Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors.
  
  
  CONCLUSIONS
  This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1.
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy giovanni.ponti@unimore.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.affiliation: Department of Genetics, University of Parma, Parma, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Martorana
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Cristel
authors.initials: C
authors.lastname: Ruini
authors.affiliation: Department of Plastic Surgery, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Loschi
authors.affiliation: Department of Plastic Surgery, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Baccarani
authors.affiliation: Department of Plastic Surgery, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: De Santis
authors.affiliation: Department of Neurosciences, University of Padua, Padova, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Pollio
authors.affiliation: Department of Genetics, University of Parma, Parma, Italy.
authors.forename: Tauro Maria
authors.initials: TM
authors.lastname: Neri
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Victor Desmond
authors.initials: VD
authors.lastname: Mandel
authors.affiliation: Department of Pathology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Maiorana
authors.affiliation: Department of Pathology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Maccio
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Maccaferri
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Tomasi
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D018318:Neurofibroma, Plexiform / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D025542:Neurofibromin 1 / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis
chemical_list: D025542:Neurofibromin 1
keywords: Elephantiasis neuromatosa; GIST; NF1 truncating mutations; Neurofibromatosis type 1; malignant peripheral nerve sheet tumors; plexiform neurofibroma