Phenotype of the C634Y mutation in the RET proto-oncogene in MEN2A: report of a family
Fenotipo de la mutación C634Y del protooncogén RET en el MEN2A: a propósito de una familia
Paula Sánchez Sobrinoa,
, Concepción Páramo Fernándeza, Pedro Gil Gilb, Beatriz Mantiñán Gila, Alberto Pérez Pedrosac, Regina Palmeiro Carballeiraa, Ricardo V. García-Mayora
Corresponding author
a Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario de Vigo, Hospital Xeral, Vigo, Pontevedra, Spain
b Servicio de Cirugía General y Digestiva, Complejo Hospitalario Universitario de Vigo, Hospital Xeral, Vigo, Pontevedra, Spain
c Servicio de Anatomía Patológica, Complejo Hospitalario Universitario de Vigo, Hospital Xeral, Vigo, Pontevedra, Spain
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García-Mayor" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Paula" "apellidos" => "Sánchez Sobrino" "email" => array:1 [ 0 => "paula_ss_82@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Concepción" "apellidos" => "Páramo Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Pedro" "apellidos" => "Gil Gil" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Beatriz" "apellidos" => "Mantiñán Gil" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Alberto" "apellidos" => "Pérez Pedrosa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "Regina" "apellidos" => "Palmeiro Carballeira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Ricardo V." "apellidos" => "García-Mayor" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario de Vigo, Hospital Xeral, Vigo, Pontevedra, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Cirugía General y Digestiva, Complejo Hospitalario Universitario de Vigo, Hospital Xeral, Vigo, Pontevedra, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Complejo Hospitalario Universitario de Vigo, Hospital Xeral, Vigo, Pontevedra, Spain" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fenotipo de la mutación C634Y del protooncogén RET en el MEN2A: a propósito de una familia" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2010-08-18" "fechaAceptado" => "2011-03-11" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec136479" "palabras" => array:2 [ 0 => "Medullary thyroid carcinoma" 1 => "Multiple endocrine neoplasia type 2" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec136480" "palabras" => array:2 [ 0 => "Carcinoma medular de tiroides" 1 => "Neoplasia endocrina múltiple 2" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Genetic testing of the RET proto-oncogene allows for early diagnosis of multiple endocrine neoplasia syndrome type 2 and establishes a correlation between genotype and clinical manifestations. The purpose of this study was to demonstrate the benefits of early diagnosis with genetic testing followed by prompt surgery for curing medullary thyroid carcinoma (MTC) as compared to later diagnosis with serum calcitonin.</p> <span class="elsevierStyleSectionTitle">Patients and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective, descriptive study of 8 members of a family with MEN 2A due to C634Y mutation. We performed serum calcitonin screening until 1999, and subsequently RET genetic testing. The carriers underwent total thyroidectomy, periodic determination of calcitonin, urinary metanephrines, calcium, and phosphorus, and cervical and abdominal imaging techniques.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Five patients were diagnosed by calcitonin familial screening and at the time of writing all of them had high calcitonin levels. Three patients were diagnosed by genetic testing (an adult and two children) and were free of disease. Calcitonin was closely monitored in the children, who underwent surgery when it started to rise at 6 and 10 years of age respectively, nodular C-cell hyperplasia having been found in both. Three of the eight carriers developed bilateral and asynchronous pheochromocytoma, half had normal urinary metanephrine levels and two also had MTC. No patient had biochemical data suggesting hyperparathyroidism although in one patient multiple parathyroid adenomas were found at thyroidectomy.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">RET genetic analysis allowed for early diagnosis and treatment with no development of MTC in our patients, gave early guidance about the type of surgery required, and allowed for genotype-phenotype correlation. It demonstrates how genetic change is associated with a pathology we can prevent and manage, thereby improving the prognosis of our patients.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Antecedentes y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El estudio genético del protooncogén RET permite un diagnóstico precoz del síndrome de neoplasia endocrina múltiple tipo 2 y establece una correlación entre el genotipo y las manifestaciones clínicas. El objetivo del presente trabajo es demostrar los beneficios del diagnóstico precoz por estudio genético seguido de tratamiento temprano en la curación del carcinoma medular de tiroides (CMT) frente al diagnóstico más tardío con la calcitonina sérica.</p> <span class="elsevierStyleSectionTitle">Pacientes y método</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio descriptivo retrospectivo de 8 miembros de una familia con MEN2A por mutación C634Y. Se realizó despistaje con calcitonina sérica hasta 1999 y estudio genético de RET posteriormente. A los portadores se les realizó tiroidectomía total y determinaciones periódicas de calcitonina, metanefrinas urinarias, calcio, fósforo y pruebas de imagen a nivel cervical y abdominal.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los 5 pacientes diagnosticados por despistaje familiar con calcitonina presentan en la actualidad cifras de calcitonina elevadas. Los 3 diagnosticados por estudio genético (un adulto y dos niños) se encuentran libres de enfermedad. En los niños se monitorizó la calcitonina y se les intervino cuando esta comenzó a elevarse, a los 6 y 10 años respectivamente, hallándose hiperplasia nodular de células C en ambos. De los 8 afectos 3 presentaron feocromocitomas, bilaterales y asincrónicos, la mitad con metanefrinas urinarias normales y dos simultáneos al CMT. Ningún paciente presentó alteraciones bioquímicas sugestivas de hiperparatiroidismo aunque en uno se descubrieron adenomas paratiroideos múltiples durante la cirugía tiroidea.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El estudio genético de RET ha conseguido el diagnóstico y tratamiento precoces y por tanto la curación del CMT en nuestros pacientes, orientándonos sobre el momento y tipo de cirugía adecuados y permitiendo correlacionar fenotipo-genotipo, ejemplificando cómo una alteración genética se asocia a patología que podemos prever y manejar mejorando el pronóstico de nuestros pacientes.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 6 | 0 | 6 |
| 2024 September | 4 | 3 | 7 |
| 2024 August | 7 | 6 | 13 |
| 2024 July | 8 | 2 | 10 |
| 2024 June | 12 | 14 | 26 |
| 2024 May | 24 | 9 | 33 |
| 2024 April | 12 | 14 | 26 |
| 2024 March | 9 | 15 | 24 |
| 2024 February | 9 | 11 | 20 |
| 2024 January | 8 | 11 | 19 |
| 2023 December | 12 | 20 | 32 |
| 2023 November | 12 | 9 | 21 |
| 2023 October | 10 | 5 | 15 |
| 2023 September | 9 | 4 | 13 |
| 2023 August | 7 | 6 | 13 |
| 2023 July | 5 | 7 | 12 |
| 2023 June | 3 | 5 | 8 |
| 2023 May | 6 | 5 | 11 |
| 2023 April | 5 | 3 | 8 |
| 2023 March | 3 | 1 | 4 |
| 2023 February | 5 | 6 | 11 |
| 2023 January | 2 | 3 | 5 |
| 2022 December | 6 | 6 | 12 |
| 2022 November | 11 | 10 | 21 |
| 2022 October | 11 | 8 | 19 |
| 2022 September | 15 | 18 | 33 |
| 2022 August | 10 | 13 | 23 |
| 2022 July | 9 | 9 | 18 |
| 2022 June | 6 | 8 | 14 |
| 2022 May | 13 | 12 | 25 |
| 2022 April | 12 | 8 | 20 |
| 2022 March | 10 | 11 | 21 |
| 2022 February | 7 | 11 | 18 |
| 2022 January | 14 | 7 | 21 |
| 2021 December | 21 | 11 | 32 |
| 2021 November | 4 | 8 | 12 |
| 2021 October | 7 | 10 | 17 |
| 2021 September | 8 | 13 | 21 |
| 2021 August | 5 | 4 | 9 |
| 2021 July | 7 | 4 | 11 |
| 2021 June | 10 | 10 | 20 |
| 2021 May | 5 | 13 | 18 |
| 2021 April | 9 | 9 | 18 |
| 2021 March | 6 | 11 | 17 |
| 2021 February | 18 | 7 | 25 |
| 2021 January | 9 | 14 | 23 |
| 2020 December | 11 | 7 | 18 |
| 2020 November | 6 | 11 | 17 |
| 2020 October | 4 | 7 | 11 |
| 2020 September | 7 | 8 | 15 |
| 2020 August | 12 | 11 | 23 |
| 2020 July | 6 | 9 | 15 |
| 2020 June | 3 | 3 | 6 |
| 2020 May | 7 | 8 | 15 |
| 2020 April | 8 | 8 | 16 |
| 2020 March | 5 | 7 | 12 |
| 2020 February | 8 | 4 | 12 |
| 2020 January | 8 | 9 | 17 |
| 2019 December | 15 | 12 | 27 |
| 2019 November | 3 | 2 | 5 |
| 2019 October | 5 | 4 | 9 |
| 2019 September | 2 | 6 | 8 |
| 2019 August | 3 | 5 | 8 |
| 2019 July | 5 | 21 | 26 |
| 2019 June | 11 | 6 | 17 |
| 2019 May | 55 | 51 | 106 |
| 2019 April | 9 | 16 | 25 |
| 2019 March | 1 | 3 | 4 |
| 2019 February | 4 | 7 | 11 |
| 2019 January | 2 | 3 | 5 |
| 2018 December | 4 | 3 | 7 |
| 2018 November | 7 | 5 | 12 |
| 2018 October | 11 | 7 | 18 |
| 2018 September | 3 | 6 | 9 |
| 2018 August | 1 | 5 | 6 |
| 2018 July | 4 | 5 | 9 |
| 2018 June | 1 | 7 | 8 |
| 2018 May | 2 | 7 | 9 |
| 2018 April | 2 | 12 | 14 |
| 2018 March | 3 | 1 | 4 |
| 2018 February | 0 | 8 | 8 |
| 2018 January | 0 | 2 | 2 |
| 2017 December | 3 | 6 | 9 |
| 2017 November | 2 | 5 | 7 |
| 2017 October | 3 | 3 | 6 |
| 2017 September | 0 | 8 | 8 |
| 2017 August | 5 | 6 | 11 |
| 2017 July | 5 | 2 | 7 |
| 2017 June | 9 | 3 | 12 |
| 2017 May | 10 | 4 | 14 |
| 2017 April | 6 | 10 | 16 |
| 2017 March | 25 | 1 | 26 |
| 2017 February | 33 | 3 | 36 |
| 2017 January | 3 | 1 | 4 |
| 2016 December | 7 | 1 | 8 |
| 2016 November | 9 | 2 | 11 |
| 2016 October | 11 | 1 | 12 |
| 2016 September | 8 | 1 | 9 |
| 2016 August | 8 | 0 | 8 |
| 2016 July | 3 | 0 | 3 |
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