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.