Endocrine Abstracts

Mutation Y791F of RET protooncogene is a well known mutation so far described in families with FMTC and familial pheochromocytoma in one family. It activates the receptor in a monomeric form. Here we present eight unrelated families with the same mutation but different fenotype expression.

Patients and methods: In last 20 years, we analyzed 216 patients with MTC (age range: 3–75 years, 45.0 mean). Genetic testing for mutation in RET proto-oncogene was performed by direct double-strand sequencing of the PCR products obtained after amplification of genomic DNAs.

Results: Of 216 patients with MTC, in 48 (22.3%) familial form of disease was found. In 23 patients (34.3%) from 8 non-related families germ-line mutation was found in c791 (Y791F). Only four had MTC and they were index cases in their families. The first two patients were diagnosed, operated and cured at the age of 33 and 42, respectively. Metastatic MTCs were diagnosed at the age of 53 in the third patient and she died at the age of 62. The fourth patient was diagnosed with metastatic MTC at the age of 62. No one had associated diseases. Nineteen patients were carriers (age range: 10–68, mean 35.7) with no evidence of the diseases but 6 of them (31.6%) had kidney development malformations. One patient had kidney hypoplasia and PHPT. She was negative for MEN1 mutations.

Conclusion: The frequency of inherited MTC in our population is in concordance with other publications, but the frequency of c791 mutation is higher than in other studies. Phenotype varies from no evidence of oncogenic activity to overt disease. While more aggressive disease has been described in patients with coexistent L769L polymorphism, the occurrence of kidney malformations may reflect the insufficient RET protein expression despite oncogenic mutation during the embryogenesis or the coexistence of other disease.