title: RET mutation Tyr791Phe: the genetic cause of different diseases derived from neural crest.
abstract: Activating germline RET mutations are presented in patients with familial medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia (MEN) types 2A and 2B, whereas inactivating germline mutations in patients with Hirschsprung's disease (HSCR). The aim of this study was to evaluate genotype-phenotype correlations of the frequently discussed Tyr791Phe mutation in exon 13 of the RET proto-oncogene. Screening of three groups of patients was performed (276 families with medullary thyroid carcinoma (MTC), 122 families with HSCR, and 29 patients with pheochromocytoma). We found this mutation in 3 families with apparently sporadic MTC, 3 families with FMTC/MEN2, 1 patient with pheochromocytoma, and 3 families with HSCR. All gene mutation carriers have a silent polymorphism Leu769Leu in exon 13. In three families second germline mutations were detected: Cys620Phe (exon 10) in MEN2A family, Met918Thr (exon 16) in MEN2B family, and Ser649Leu (exon 11) in HSCR patient. Detection of the Tyr791Phe mutation in MEN2/MTC and also in HSCR families leads to the question whether this mutation has a dual character (gain-of-function as well as loss-of-function). A rare case of malignant pheochromocytoma in a patient with the Tyr791Phe mutation is presented. This study shows various clinical characteristics of the frequently discussed Tyr791Phe mutation.
authors.affiliation: Department of Molecular Endocrinology, Institute of Endocrinology, Narodni 8, 116 94, Prague 1, Czech Republic. evaclavikova@endo.cz
authors.forename: Eliska
authors.initials: E
authors.lastname: Vaclavikova
authors.forename: Sarka
authors.initials: S
authors.lastname: Dvorakova
authors.forename: Vlasta
authors.initials: V
authors.lastname: Sykorova
authors.forename: Radovan
authors.initials: R
authors.lastname: Bilek
authors.forename: Katerina
authors.initials: K
authors.lastname: Dvorakova
authors.forename: Petr
authors.initials: P
authors.lastname: Vlcek
authors.forename: Richard
authors.initials: R
authors.lastname: Skaba
authors.forename: Tomas
authors.initials: T
authors.lastname: Zelinka
authors.forename: Bela
authors.initials: B
authors.lastname: Bendlova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D018276:Carcinoma, Medullary / Q000235:genetics; D002648:Child; D004194:Disease / Q000235:genetics*; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D018095:Germ-Line Mutation; D006627:Hirschsprung Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics; D009432:Neural Crest / Q000473:pathology*; D010649:Phenylalanine / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics; D014443:Tyrosine / Q000235:genetics; D055815:Young Adult
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014443:Tyrosine; D010649:Phenylalanine; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human