RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant

Background. The aim of this study was to identify germline mutation of the RET (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. Methods/Patients. We exami...

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Autores principales:	Elia Damavandi, Fatemeh Vand-Rajabpour, Maliheh Javadi-Arjmand, Mohammad-Reza Mohajeri Tehrani, Bagher Larijani, Majid Kabuli, Mohsen Ghadami
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/82f3d9f00aea4c63b33dc8a6ba3b5de4
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spelling	oai:doaj.org-article:82f3d9f00aea4c63b33dc8a6ba3b5de42021-11-15T01:19:16ZRET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant2042-007210.1155/2021/7250870https://doaj.org/article/82f3d9f00aea4c63b33dc8a6ba3b5de42021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/7250870https://doaj.org/toc/2042-0072Background. The aim of this study was to identify germline mutation of the RET (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. Methods/Patients. We examined all six hot spot exons (exons 10, 11, 13, and 14–16) of the RET gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases. First-degree relatives of RET positive cases were also genotyped for index mutation. Moreover, presymptomatic carriers were referred to the endocrinologist for further clinical management and prophylactic thyroidectomy if needed. Results. Overall, the genetic status of all of the participants was determined by RET mutation screening, including 61 affected individuals, 22 presymptomatic carriers, and 29 genetically healthy subjects. In 37.5% (17 of 45) of the MTC referral index patients, 8 distinct RET germline mutations were found, including p.C634R (35.3%), p.M918T (17.6%), p.C634Y (11.8%), p.C634F (5.9%), p.C611Y (5.9%), p.C618R (5.9%), p.C630R (5.9%), p.L790F (5.9%), and one uncertain variant p.V648I (5.9%). Also, we found a novel variant p.H648R in one of our apparently sporadic patients. Conclusion. RET mutation detection is a promising/golden screening test and provides an accurate presymptomatic diagnostic test for at-risk carriers (the siblings and offspring of the patients) to consider prophylactic thyroidectomy. Thus, according to the ATA recommendations, the screening of the RET proto-oncogene is indicated for patients with MTC.Elia DamavandiFatemeh Vand-RajabpourMaliheh Javadi-ArjmandMohammad-Reza Mohajeri TehraniBagher LarijaniMajid KabuliMohsen GhadamiHindawi LimitedarticleDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENJournal of Thyroid Research, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	Diseases of the endocrine glands. Clinical endocrinology RC648-665 Elia Damavandi Fatemeh Vand-Rajabpour Maliheh Javadi-Arjmand Mohammad-Reza Mohajeri Tehrani Bagher Larijani Majid Kabuli Mohsen Ghadami RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant
description	Background. The aim of this study was to identify germline mutation of the RET (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. Methods/Patients. We examined all six hot spot exons (exons 10, 11, 13, and 14–16) of the RET gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases. First-degree relatives of RET positive cases were also genotyped for index mutation. Moreover, presymptomatic carriers were referred to the endocrinologist for further clinical management and prophylactic thyroidectomy if needed. Results. Overall, the genetic status of all of the participants was determined by RET mutation screening, including 61 affected individuals, 22 presymptomatic carriers, and 29 genetically healthy subjects. In 37.5% (17 of 45) of the MTC referral index patients, 8 distinct RET germline mutations were found, including p.C634R (35.3%), p.M918T (17.6%), p.C634Y (11.8%), p.C634F (5.9%), p.C611Y (5.9%), p.C618R (5.9%), p.C630R (5.9%), p.L790F (5.9%), and one uncertain variant p.V648I (5.9%). Also, we found a novel variant p.H648R in one of our apparently sporadic patients. Conclusion. RET mutation detection is a promising/golden screening test and provides an accurate presymptomatic diagnostic test for at-risk carriers (the siblings and offspring of the patients) to consider prophylactic thyroidectomy. Thus, according to the ATA recommendations, the screening of the RET proto-oncogene is indicated for patients with MTC.
format	article
author	Elia Damavandi Fatemeh Vand-Rajabpour Maliheh Javadi-Arjmand Mohammad-Reza Mohajeri Tehrani Bagher Larijani Majid Kabuli Mohsen Ghadami
author_facet	Elia Damavandi Fatemeh Vand-Rajabpour Maliheh Javadi-Arjmand Mohammad-Reza Mohajeri Tehrani Bagher Larijani Majid Kabuli Mohsen Ghadami
author_sort	Elia Damavandi
title	RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant
title_short	RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant
title_full	RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant
title_fullStr	RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant
title_full_unstemmed	RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant
title_sort	ret proto-oncogene mutational analysis in 45 iranian patients affected with medullary thyroid carcinoma: report of a new variant
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/82f3d9f00aea4c63b33dc8a6ba3b5de4
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RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant

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