title: Patient affected by neurofibromatosis type 1 and thyroid C-cell hyperplasia harboring pathogenic germ-line mutations in both NF1 and RET genes.
abstract: Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease with an estimated incidence of 1 in 3000/3500 live births. NF1 is caused by a mutation in a gene which encodes a protein known as neurofibromin. In up to 5% of cases, NF1 is associated with pheochromocytomas. RET proto-oncogene encodes a member of the receptor tyrosine kinase family involved in the normal development or the neoplastic growth of neural crest cell lineages. Germ-line RET mutations account for cases of Multiple Endocrine Neoplasia type 2 (MEN2), an autosomal dominant genetic syndrome where medullary thyroid carcinoma (MTC) is the major and more clinically severe feature, with nearly complete penetrance. C-cell hyperplasia (CCH) is described in MEN2 patients, and it has been implicated as the precursor of in situ MTC. Patients with RET mutations develop pheochromocytomas in 50% of cases. Rarely, patients with NF1 have been found to present, in addition to the NF1 clinical picture, other lesions, such as parathyroid hyperplasia/adenoma and/or medullary thyroid carcinoma. In spite of the presence of these MEN2 lesions, in none of these patients mutations of gene RET have been found so far. In this report, we describe the first case of a patient affected by a germ-line mutation in both NF1 and RET genes.
authors.affiliation: Endocrinology Unit, Careggi Hospital, Azienda Ospedaliera Universitaria Careggi, Florence, Italy. Electronic address: tonino.ercolino@unifi.it.
authors.forename: Tonino
authors.initials: T
authors.lastname: Ercolino
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Azienda Ospedaliera Universitaria, Sassari, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lai
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Valentino
authors.initials: V
authors.lastname: Giachè
authors.affiliation: Medical Genetic Unit, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Melchionda
authors.affiliation: Medical Genetic Unit, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Azienda Ospedaliera Universitaria, Sassari, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Delitala
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; Istituto Toscano Tumori, Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Azienda Ospedaliera Universitaria, Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fanciulli
mesh_terms: D018278:Carcinoma, Neuroendocrine; D005260:Female; D016514:Genes, Neurofibromatosis 1; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D050033:Thyroid Dysgenesis / Q000235:genetics* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: C-cell hyperplasia; C-cells; CCH; CT; MEN2; MTC; Multiple Endocrine Neoplasia type 2; NF1; NF1 gene; Neurofibromatosis type 1; PKA; RET gene; Thyroid C-cell hyperplasia; calcitonin; medullary thyroid carcinoma; neurofibromatosis type 1; parafollicular cells; protein kinase A