Mutational analysis of the RET proto-oncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung's disease.

BACKGROUND/PURPOSE: Germline mutations of the RET proto-oncogene (RET; 10q11.2) have been reported in multiple endocrine neoplasia type 2A (MEN 2A) and Hirschsprung's disease. The authors investigated a Japanese kindred in which MEN 2A and Hirschsprung's disease frequently have been found. METHODS: The pedigree consisted of 28 members (11 boys and 17 girls) spanning 4 generations, of whom, 8 were affected with MEN 2A or Hirschsprung's disease. RESULTS: Direct sequence DNA analysis of the RET proto-oncogene showed a heterozygosity for a G to C transition at the second nucleotide of codon 620 (exon 10) in the patients, resulting in the replacement of cysteine by a serine residue in the affected Ret protein. This family added a novel RET missense mutation (C620S) predisposing to the association of MEN 2A and Hirschsprung's disease. CONCLUSION: Detection of the mutated RET gene carriers may be used for genetic counseling of potential risk for Hirschsprung's disease as well as MEN 2A in the affected families.