RET MUTATIONS IN EXON-13 AND EXON-14 OF FMTC PATIENTS

RET is a receptor tyrosine kinase gene which is responsible for three different inherited cancer syndromes namely multiple endocrine neoplas ia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid c arcinoma (FMTC) as web as for Hirschsprung disease (HSCR), a congenita l disorder affecting the intestinal motility. Germ-line mutations in t he RET exons 10 and 11 were demonstrated in the majority of the MEN 2A and FMTC patients, On the other hand, one codon of RET exon 16 is pre ferentially changed in MEN 2B patients, Recently, a germ-line mutation in the exon 13 was described in one FMTC family as well as in four sp oradic MTCs. In the present study, we observed the same exon 13 mutati on in two FMTC families. In addition, we identified a previously unrep orted substitution of RET exon 14 in two unrelated FMTC families. Both mutations segregate with the disease in these four FMTC families and involve the tyrosine kinase domain of RET. Haplotype analysis using po lymorphic markers tightly Linked to the RET gene indicates that in eac h pedigree the mutation arose as an independent event.