Genotype-phenotype correlations in Hungarian patients with hereditary medullary thyroid cancer

The genotype and phenotype characteristics of Hungarian patients with RET proto-oncogene mutations operated on for hereditary medullary thyroid cancer (MTC) were studied. The genetic screening was performed in two centers and 40 patients with hereditary MTC or C-cell hyperplasia (CCH) from 18 unrelated families were analyzed. One patient having a mutation in exon 16 (Met918Thr) presented with the MEN2B phenotype, six patients from two families had hereditary MTC without pheochromocytoma (pheo) and primary hyperparathyroidism (PHPT), whereas 33 patients from 15 families showed the MEN2A phenotype. Two different mutations were identified in exon 10 (Cys609Tyr and Cys609Ser), five different mutations were present in exon 11 (Cys634Phe, Cys634Arg, Cys634Tyr, Cys634Trp and Cys634Ser), and two different mutations were localized in exon 14 (Val804Met and Val804Leu). Mutations in exon 10 were associated with hereditary MTC (Cys609Tyr) or with MEN2A syndrome (Cys609Ser). Mutations in exon 11 were always associated with the MEN2A phenotype. PHPT was present in one patient with mutation in exon 14 (Val804Met), whereas all other patients affected with mutations in exon 14 had hereditary MTC without PHPT and/or pheos.