Germline founder variant c.1998delinsTTCT in the RET oncogene: a cohort study in 15 Belgian families
Authors' conclusion
The c.1998delinsTTCT variant in the RET gene is pathogenic and associated with a moderate risk for medullary thyroid carcinoma and rarely with other multiple endocrine neoplasia type 2A (MEN2A) manifestations. Active surveillance is a possible option in heterozygous gene carriers with a negative first clinical evaluation.
Study context
- Population
- Index patients and predictive carriers of the RET c.1998delinsTTCT (codon 666) variant identified through familial cascade testing, Belgium, 2001–2020
- Participants
- 119 patients
- Exposure
- Index vs Heterozygous carriers vs Homozygous carriers
- Indexn = 15
- Heterozygous carriersn = 102
- Homozygous carriersn = 2
- Outcome
- Clinical phenotype and age-dependent penetrance in predictive variant carriers
Methodological detailsfamilial cascade testing, 15 Belgian families
- Familial cascade testing
- 15 Belgian families
Main finding
As reported in the abstract
Age-dependent penetrance in heterozygous carriers
- Median age at developing high suspicion of disease (range 7-75)
- 52 years
- Predicted penetrance at age 70 years (9% SE)
- 62%
- High suspicion of clinical disease at initial evaluation
- 25 patients
- High suspicion of clinical disease during follow-up
- 3 patients
- No high suspicion during surveillance
- 56 patients
- Did not proceed to screening
- 18 patients
Observational data: associations, not effects.
Further findings
Surgically treated heterozygous carriers vs index patients
- Lower presurgical basal calcitonin, lower disease stage, less need for adjuvant therapy and higher chances of remission in surgically treated heterozygous carriers vs index patients
Other MEN2A manifestations
- Pheochromocytoma
- 2 patients
- PHPT
- 1 patient
Homozygous carriers · first clinical evaluation
- Higher disease severity at first clinical evaluation in the 2 homozygous carriers
Original publication
Germline founder variant c.1998delinsTTCT in the RET oncogene: a cohort study in 15 Belgian families. Eur J Endocrinol. Published 15 September 2023. doi:10.
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