A Homozygous RET K666N Genotype with an MEN2A Phenotype

Tania Jaber, Samuel M. Hyde, Gilbert J. Cote, Elizabeth G. Grubbs, Wesley Giles, Cathy A. Stevens, Ramona Dadu

Research output: Contribution to journalArticle

Abstract

Context Germline RET K666N mutation has been described as a pathogenic mutation with low disease penetrance for medullary thyroid cancer (MTC) without other features of multiple endocrine neoplasia type 2A. We describe a patient with homozygous RET K666N mutation with MTC and bilateral pheochromocytoma (PHEO). Case Description A 59-year-old woman received a diagnosis of MTC after biopsy of two thyroid nodules. Coincident biochemical and radiologic testing was suspicious for bilateral PHEO, confirmed after bilateral adrenalectomy. There was no evidence of primary hyperparathyroidism (PHPT). She had a total thyroidectomy with neck dissection revealing bilateral MTC with lymph node metastases. Germline RET testing identified homozygous K666N mutations. Genetic testing of family members showed that both adult children harbor a heterozygous K666N mutation. Her 32-year-old son had an elevated calcitonin level and underwent thyroidectomy, which identified MTC. Her 30-year-old daughter had a normal calcitonin level. Prophylactic thyroidectomy showed C-cell hyperplasia only. Three of seven other family members were tested and found to carry the mutation. All had normal calcitonin levels, and none had biochemical evidence of PHEO or PHPT. Given the absence of PHEO in reported RET K666N families, our proband underwent genetic testing for causes of hereditary paragangliomas or PHEO. No additional mutations were identified. Conclusions Here we report a case of a homozygous RET K666N mutation leading to coincident MTC and PHEO. Heterozygous presentations of RET K666N mutations have low penetrance for isolated MTC. We believe that the gene dosage associated with the homozygosity of this variant contributed to the occurrence of bilateral PHEO.

Original languageEnglish (US)
Pages (from-to)1269-1272
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Pheochromocytoma
Calcitonin
Genotype
Phenotype
Mutation
Testing
Thyroidectomy
Dissection
Biopsy
Primary Hyperparathyroidism
Penetrance
Ports and harbors
Genetic Testing
Nuclear Family
Genes
Multiple Endocrine Neoplasia Type 2a
Paraganglioma
Thyroid Nodule
Neck Dissection
Gene Dosage

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Jaber, T., Hyde, S. M., Cote, G. J., Grubbs, E. G., Giles, W., Stevens, C. A., & Dadu, R. (2018). A Homozygous RET K666N Genotype with an MEN2A Phenotype. Journal of Clinical Endocrinology and Metabolism, 103(4), 1269-1272. https://doi.org/10.1210/jc.2017-02402

A Homozygous RET K666N Genotype with an MEN2A Phenotype. / Jaber, Tania; Hyde, Samuel M.; Cote, Gilbert J.; Grubbs, Elizabeth G.; Giles, Wesley; Stevens, Cathy A.; Dadu, Ramona.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 103, No. 4, 01.04.2018, p. 1269-1272.

Research output: Contribution to journalArticle

Jaber, T, Hyde, SM, Cote, GJ, Grubbs, EG, Giles, W, Stevens, CA & Dadu, R 2018, 'A Homozygous RET K666N Genotype with an MEN2A Phenotype', Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 4, pp. 1269-1272. https://doi.org/10.1210/jc.2017-02402
Jaber, Tania ; Hyde, Samuel M. ; Cote, Gilbert J. ; Grubbs, Elizabeth G. ; Giles, Wesley ; Stevens, Cathy A. ; Dadu, Ramona. / A Homozygous RET K666N Genotype with an MEN2A Phenotype. In: Journal of Clinical Endocrinology and Metabolism. 2018 ; Vol. 103, No. 4. pp. 1269-1272.
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abstract = "Context Germline RET K666N mutation has been described as a pathogenic mutation with low disease penetrance for medullary thyroid cancer (MTC) without other features of multiple endocrine neoplasia type 2A. We describe a patient with homozygous RET K666N mutation with MTC and bilateral pheochromocytoma (PHEO). Case Description A 59-year-old woman received a diagnosis of MTC after biopsy of two thyroid nodules. Coincident biochemical and radiologic testing was suspicious for bilateral PHEO, confirmed after bilateral adrenalectomy. There was no evidence of primary hyperparathyroidism (PHPT). She had a total thyroidectomy with neck dissection revealing bilateral MTC with lymph node metastases. Germline RET testing identified homozygous K666N mutations. Genetic testing of family members showed that both adult children harbor a heterozygous K666N mutation. Her 32-year-old son had an elevated calcitonin level and underwent thyroidectomy, which identified MTC. Her 30-year-old daughter had a normal calcitonin level. Prophylactic thyroidectomy showed C-cell hyperplasia only. Three of seven other family members were tested and found to carry the mutation. All had normal calcitonin levels, and none had biochemical evidence of PHEO or PHPT. Given the absence of PHEO in reported RET K666N families, our proband underwent genetic testing for causes of hereditary paragangliomas or PHEO. No additional mutations were identified. Conclusions Here we report a case of a homozygous RET K666N mutation leading to coincident MTC and PHEO. Heterozygous presentations of RET K666N mutations have low penetrance for isolated MTC. We believe that the gene dosage associated with the homozygosity of this variant contributed to the occurrence of bilateral PHEO.",
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AU - Jaber, Tania

AU - Hyde, Samuel M.

AU - Cote, Gilbert J.

AU - Grubbs, Elizabeth G.

AU - Giles, Wesley

AU - Stevens, Cathy A.

AU - Dadu, Ramona

PY - 2018/4/1

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N2 - Context Germline RET K666N mutation has been described as a pathogenic mutation with low disease penetrance for medullary thyroid cancer (MTC) without other features of multiple endocrine neoplasia type 2A. We describe a patient with homozygous RET K666N mutation with MTC and bilateral pheochromocytoma (PHEO). Case Description A 59-year-old woman received a diagnosis of MTC after biopsy of two thyroid nodules. Coincident biochemical and radiologic testing was suspicious for bilateral PHEO, confirmed after bilateral adrenalectomy. There was no evidence of primary hyperparathyroidism (PHPT). She had a total thyroidectomy with neck dissection revealing bilateral MTC with lymph node metastases. Germline RET testing identified homozygous K666N mutations. Genetic testing of family members showed that both adult children harbor a heterozygous K666N mutation. Her 32-year-old son had an elevated calcitonin level and underwent thyroidectomy, which identified MTC. Her 30-year-old daughter had a normal calcitonin level. Prophylactic thyroidectomy showed C-cell hyperplasia only. Three of seven other family members were tested and found to carry the mutation. All had normal calcitonin levels, and none had biochemical evidence of PHEO or PHPT. Given the absence of PHEO in reported RET K666N families, our proband underwent genetic testing for causes of hereditary paragangliomas or PHEO. No additional mutations were identified. Conclusions Here we report a case of a homozygous RET K666N mutation leading to coincident MTC and PHEO. Heterozygous presentations of RET K666N mutations have low penetrance for isolated MTC. We believe that the gene dosage associated with the homozygosity of this variant contributed to the occurrence of bilateral PHEO.

AB - Context Germline RET K666N mutation has been described as a pathogenic mutation with low disease penetrance for medullary thyroid cancer (MTC) without other features of multiple endocrine neoplasia type 2A. We describe a patient with homozygous RET K666N mutation with MTC and bilateral pheochromocytoma (PHEO). Case Description A 59-year-old woman received a diagnosis of MTC after biopsy of two thyroid nodules. Coincident biochemical and radiologic testing was suspicious for bilateral PHEO, confirmed after bilateral adrenalectomy. There was no evidence of primary hyperparathyroidism (PHPT). She had a total thyroidectomy with neck dissection revealing bilateral MTC with lymph node metastases. Germline RET testing identified homozygous K666N mutations. Genetic testing of family members showed that both adult children harbor a heterozygous K666N mutation. Her 32-year-old son had an elevated calcitonin level and underwent thyroidectomy, which identified MTC. Her 30-year-old daughter had a normal calcitonin level. Prophylactic thyroidectomy showed C-cell hyperplasia only. Three of seven other family members were tested and found to carry the mutation. All had normal calcitonin levels, and none had biochemical evidence of PHEO or PHPT. Given the absence of PHEO in reported RET K666N families, our proband underwent genetic testing for causes of hereditary paragangliomas or PHEO. No additional mutations were identified. Conclusions Here we report a case of a homozygous RET K666N mutation leading to coincident MTC and PHEO. Heterozygous presentations of RET K666N mutations have low penetrance for isolated MTC. We believe that the gene dosage associated with the homozygosity of this variant contributed to the occurrence of bilateral PHEO.

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