PURPOSE: The RET proto-oncogene is involved in neural crest disorders. 
Activating germline mutations in the RET proto-oncogene cause the development of 
familial medullary thyroid carcinoma (FMTC) or medullary thyroid carcinoma (MTC) 
as a part of multiple endocrine neoplasia type 2 (MEN2) syndrome. Inactivating 
germline mutations in the RET proto-oncogene are detected in Hirschsprung's 
disease (HSCR). Only in a very small number of families are these 2 diseases 
expressed together.
METHODS: This study presents a novel Czech kindred with FMTC-HSCR phenotype. Two 
family members (mother and daughter) were tested for RET germline mutations in 
exons 10, 11, 13, 14, 15, and 16.
RESULTS: Direct fluorescent sequencing of genomic DNA revealed a heterozygous 
mutation in the RET proto-oncogene in exon 10 at codon C609Y in both persons 
tested. This family was reclassified, thanks to genetic screening from the 
apparently sporadic MTC-HSCR to FMTC-HSCR.
CONCLUSION: The germline mutation was detected because of the systematic genetic 
screening of the RET proto-oncogene, which is useful for genetic counseling of 
potential risk of HSCR and MTC in other family members. This family could be 
added to the small worldwide cohort of families with MEN2A/FMTC-HSCR.