A NEW INHERITED RET PROTOONCOGENE MUTATION ASSOCIATED WITH FAMILIAL MEDULLARY-THYROID CARCINOMA AND POLYMORPHISMS IN THE ADJACENT REGIONS

A new point mutation, TCG(Ser) --> GCG(Ala) in codon 891, exon 15 of t he RET protooncogene was revealed in two patients from a pedigree with familial medullary thyroid carcinoma (FMTC), but not in healthy perso ns. A linkage analysis with two well-known and two new intragene polym orphisms showed that informative polymorphic markers, the phenotypic e xpression of the disease, and the mutation are cosegregated in the stu died pedigree, Two new polymorphisms, G/A at position -24 of intron 14 and C/T in codon 836 of exon 14, were found in the RET protooncogene. The frequencies of allele 1 of the polymorphic site in codon 836 were the same (0.96) in the Russian and German populations. This was also characteristic of two polymorphisms revealed earlier, namely, the site s in codons 691 (0.80 and 0.81, respectively) and 904 (0.21 and 0.22). However, the frequency of allele 1 of the polymorphisms in intron 14 differed significantly (0.87 and 0.77, respectively).