Purpose: The RET proto-oncogene is involved in neural crest disorders. Activa ting germline mutations in the RET protooncogene cause the development of famili al medullary thyroid carcinoma (FMTC) or medullary thyroid carcinoma (MTC) as a part of multiple endocrine neoplasia type 2 (MEN2) syndrome. Inactivating germli nemutations 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 to gether. Methods: This study presents a novel Czech kindred with FMTC-HSCR pheno type. Two family members (mother and daughter) were tested for RET germline muta tions in exons 10, 11, 13, 14, 15, and 16. Results: Direct fluorescent sequencin g 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, tha nks to genetic screening from the apparently sporadic MTC-HSCR to FMTC-HSCR. C onclusion: 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 add ed to the small worldwide cohort of families with MEN2A/FMTC-HSCR.
展开▼
