Background: According to current guidelines, RET mutation screening is indicated for MEN2 and familial MTC (FMTC) kindreds, as well as for apparently sporadic MTC patients.
Aim: To investigate RET mutations in Romanian MEN2, FMTC and sporadic MTC cases.
Patients and methods: RET mutation screening was performed by high-resolution melting analysis followed by direct sequencing of PCR products of exons 10-11 in 7 MEN2A families, 2 FMTC families and 25 apparently sporadic MTC patients.
Results: In all MEN2A families (27 tested individuals) a RET mutation was present (4 Cys634Trp and 3 Cys634Arg). All subjects with clinical or biochemical disease (15) were positive for RET mutation. 5 asymptomatic carriers were identified and 7 subjects at risk were negative for their respective family mutations. Prophylactic thyroidectomy was proposed to asymptomatic carriers and to pheochromocytoma-only individuals. Five subjects accepted and three denied thyroidectomy. In one FMTC family we found a Cys634Tyr mutation in 2 affected individuals, while in the other FMTC family there was no RET mutation (3 individuals tested). Only one sporadic MTC patient had a RET mutation (Cys634Arg). Screening for this mutation in the patients family is pending.
Discussion: We detected a low number of asymptomatic mutation carriers, mainly because of poor acceptance of screening by non-affected individuals.
Conclusions: RET mutation screening should be performed in MEN2 / FMTC families and sporadic MTC. We are extending screening to exons 1316 in our sporadic MTC cohort.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology