Objective HSCR is a congenital inherited disease characterized by the absence of ganglia in gastrointestinal tract. The major genetic cause are mutations in the RET proto-oncogene that are in exon 10 also associated with medullary thyroid carcinoma (MTC). The aim of the study was to screen RET gene and to find the risk of MTC in patients with HSCR.

Methods The genetic analysis comprised 109 HSCR patients - 73 classical HSCR, 15 long colonic aganglionosis, 16 total colonic aganglionosis and 5 nearly total bowel aganglionosis. DNAs were isolated from blood after signing informed consent approved by ethical committee. HSCR patients were tested for RET genetic changes in exons 2–21 (single strand conformation polymorphism and sequencing methods).

Results Found RET mutations: Val373Ala (exon 6), del603(A), Cys609Tyr, Cys620Arg (exon 10), Ser649Leu (exon 11), Gly798Ser, Tyr791Phe (exon 13). Found RET polymorphisms: in 81% Ala45 (exon 2), in 3% Val125 (exon 3), in 42% Ala432 (exon 7), in 16% Gly691Ser (exon 11), in 64% Leu769 (exon 13), in 4% Ser836 (exon 14), in 33% IVS14-24G>A (intron 14), in 17% Ser904 (exon 15) and in 46% IVS20-133T>C (intron 20). Genetic screening revealed RET mutations in 8 (7.3%) HSCR patients, the co-occurrence with MTC was found in 2 families, 2 mutations with potential MTC risk and 3 new RET mutations were detected.

Conclusions We recommend screening all RET exons in HSCR patients and in cases with detected mutations visiting endocrinologists for possible risk of MTC. Supported by grant GACR301/06/P425.