Codon Y791F mutations in a large kindred: is prophylactic thyroidectomy always indicated?

Area of Science:

• Genetics
• Oncology
• Endocrinology

Background:

• RET proto-oncogene mutations are typically associated with medullary thyroid carcinomas.
• Preventive thyroidectomy is usually recommended for individuals carrying these mutations.
• A Danish family with the Y791F RET mutation presented without medullary thyroid carcinomas, challenging typical associations.

Purpose of the Study:

• To investigate the penetrance of the Y791F RET proto-oncogene mutation in a large kindred.
• To assess the clinical manifestation of the Y791F mutation in gene carriers.
• To evaluate the necessity of prophylactic thyroidectomy in individuals with this specific mutation.

Main Methods:

• Genetic screening of 27 family members for the Y791F RET mutation.
• Pentagastrin testing and serum calcitonin measurements in gene carriers.
• Mutation analysis using direct bidirectional sequencing on an ABI 3100 Genetic Analyzer.

Main Results:

• Twelve out of 27 (44.4%) family members carried the Y791F RET mutation.
• None of the gene carriers exhibited abnormal pentagastrin test results.
• No significant difference in basal serum calcitonin levels was observed between carriers and non-carriers.
• No signs of primary hyperparathyroidism or phaeochromocytoma were detected in carriers.

Conclusions:

• The Y791F RET proto-oncogene mutation appears to have low penetrance.
• Watchful waiting with repeated pentagastrin testing may be a viable alternative to prophylactic thyroidectomy in selected cases.
• Careful risk-benefit evaluation is crucial when considering management strategies for this mutation.