BACKGROUND: RET germline mutations predispose to the development of inherited 
cancer syndrome multiple endocrine neoplasia type 2 (MEN2). Several variants of 
the RET proto-oncogene including G691S and S904S have been suggested to act as 
genetic modifiers at the age of onset ofMEN2.
AIM: The aim of this study is to characterize clinically and molecularly 7 
Cypriot patients with familial medullary thyroid carcinoma (FMTC) and 1 with 
MEN2A and also to determine the allelic frequencies of the RET variants G691S 
and S904S.
SUBJECTS AND METHODS: Seven probands from FMTC families and 1 from MEN2A were 
screened for the presence of RET mutations and the G691S and S904S variants. 
Additionally, 226 healthy Cypriots, who served as controls were analysed in an 
attempt to compare the frequencies of G691S and S904S RET variants to those 
observed in the 8 patients.
RESULTS: The clinical diagnosis of the probands was based on clinical 
presentation and supported with biochemical findings. The germline C618R 
mutation of exon 10 was identified in all 8 probands and in 15 relatives from 7 
different families. No significant difference in the G691S/S904S variants allele 
frequencies between patients (4/16 or 25%) and controls (124/452 or 27.4%) was 
found.
CONCLUSIONS: Mutational screening of the RET gene identified a common mutation 
(C618R) in all 8 (7 FMTC and 1 MEN2A) unrelated Cypriot patients which may be 
explained by a founder effect. Additionally, no association of the G691S/S904S 
variants was linked with the disease.