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.