Hirschsprung's disease and medullary thyroid carcinoma: 15-year experience with molecular genetic screening of the RET proto-oncogene
Language English Country Germany Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Time Factors MeSH
- Adult MeSH
- Genetic Testing methods MeSH
- Hirschsprung Disease complications diagnosis genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Mutation * MeSH
- DNA Mutational Analysis MeSH
- Thyroid Neoplasms complications diagnosis genetics MeSH
- Follow-Up Studies MeSH
- Carcinoma, Neuroendocrine MeSH
- Prospective Studies MeSH
- Proto-Oncogene Mas MeSH
- Proto-Oncogene Proteins c-ret genetics MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Pedigree MeSH
- Aged, 80 and over MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- MAS1 protein, human MeSH Browser
- Proto-Oncogene Mas MeSH
- Proto-Oncogene Proteins c-ret MeSH
PURPOSE: Inactivating germline mutations in the RET proto-oncogene are the major genetic cause of Hirschsprung's disease (HD). In some cases, HD can be associated with medullary thyroid carcinoma (MTC) that is commonly caused by activating RET mutations. METHODS: The retrospective and prospective genetic analyses of 157 patients with HD operated on between December 1979 and June 2011 were carried out. DNA was isolated from peripheral leukocytes. HD patients and family members were tested for RET mutations by direct sequencing and single-strand conformation polymorphism methods. RESULTS: RET mutations were detected in 16 patients (10%). Association with MTC was found in two families, other eight families had a mutation with potentially high risk of MTC development and four novel mutations were detected. Total colonic aganglionosis was noted to have a high mutation detection rate (40%). Three patients underwent total thyroidectomy (two had clinical manifestation of MTC, one C-cell hyperplasia). CONCLUSION: Results show the benefit of systematic RET mutation screening in HD patients in order to identify the risk of MTC in the preclinical stage of the disease. All patients should be tested for RET mutations at least in exon 10, and now additionally in exon 11 and 13, as well.
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