Clinical spectrum of MEN2A in a large family caused by the infrequent RET mutation Cys609Phe

Authors

  • J Oriola,

    Corresponding author
    • Servei de Bioquímica i Genètica Molecular, CDB, Hospital Clínic, University of Barcelona, Barcelona, Spain
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  • J Biarnes,

    1. Unitat d'Endocrinologia, Diabetis i Nutrició (UDENTG), CIBEROBN, Hospital Dr Josep Trueta, Girona, Spain
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  • C Hernandez,

    1. CIBERDEM (CIBER de Diabetes y Enfermedades Metabólicas Asociadas), Instituto de Salud Carlos III, Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
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  • R Simó

    1. CIBERDEM (CIBER de Diabetes y Enfermedades Metabólicas Asociadas), Instituto de Salud Carlos III, Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
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  • The authors stated that there are no conflicts of interest regarding the publication of this article.

Corresponding author: Dr Josep Oriola, Servei de Bioquímica i Genètica Molecular, CDB, Hospital Clínic, University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain.

Tel.: +34 932275510;

fax: +34 932275697;

e-mail: joriola@clinic.ub.es

Abstract

Mutations in RET proto-oncogene cause multiple endocrine neoplasia 2A (MEN2A). Mutations in codons 609 and 611 are not frequent. We identified two MEN2A families with the Cys609Phe RET mutation, which turned out to be the same family. This mutation has been described a couple of times with no clinical details. We have characterized the clinical phenotype of this large kindred. A 54-year-old woman, with a medullary thyroid carcinoma (MTC), and a 33-year-old woman, who was operated on for an adrenal pheochromocytoma, were the index cases. 35 relatives were studied. Sixteen turned out to be carriers and 12 of them have been operated on. This family showed eight patients with C-cell hyperplasia, six patients affected by MTC and two showing pheochromocytoma. A papillary thyroid carcinoma was also found, together with the MTC, in one of the carriers. The phenotype in this large kindred is clearly of MEN2A. In carriers presenting the Cys609Phe mutation, the timing of the presentation of the syndrome is highly unpredictable. Therefore, a strict follow up of MTC must be carried out because of risk, and pheochromocytoma should not be ignored. These results reinforce the scarce data observed on this particular mutation.

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