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RET mutation Tyr791Phe: the genetic cause of different diseases derived from neural crest

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Abstract

Activating germline RET mutations are presented in patients with familial medullary thyroid carcinoma (FMTC) and multiple endocrine neoplasia (MEN) types 2A and 2B, whereas inactivating germline mutations in patients with Hirschsprung’s disease (HSCR). The aim of this study was to evaluate genotype–phenotype correlations of the frequently discussed Tyr791Phe mutation in exon 13 of the RET proto-oncogene. Screening of three groups of patients was performed (276 families with medullary thyroid carcinoma (MTC), 122 families with HSCR, and 29 patients with pheochromocytoma). We found this mutation in 3 families with apparently sporadic MTC, 3 families with FMTC/MEN2, 1 patient with pheochromocytoma, and 3 families with HSCR. All gene mutation carriers have a silent polymorphism Leu769Leu in exon 13. In three families second germline mutations were detected: Cys620Phe (exon 10) in MEN2A family, Met918Thr (exon 16) in MEN2B family, and Ser649Leu (exon 11) in HSCR patient. Detection of the Tyr791Phe mutation in MEN2/MTC and also in HSCR families leads to the question whether this mutation has a dual character (gain-of-function as well as loss-of-function). A rare case of malignant pheochromocytoma in a patient with the Tyr791Phe mutation is presented. This study shows various clinical characteristics of the frequently discussed Tyr791Phe mutation.

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Acknowledgment

The study was supported by GACR 301/06/P425 and IGA MH CR NR/9165-3.

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Authors and Affiliations

  1. Department of Molecular Endocrinology, Institute of Endocrinology, Narodni 8, 116 94, Prague 1, Czech Republic

    Eliska Vaclavikova, Sarka Dvorakova, Vlasta Sykorova & Bela Bendlova

  2. Department of Proteohormones and Biofactors, Institute of Endocrinology, Narodni 8, 116 94, Prague 1, Czech Republic

    Radovan Bilek

  3. Department of Clinical Endocrinology, Institute of Endocrinology, Narodni 8, 116 94, Prague 1, Czech Republic

    Katerina Dvorakova

  4. Department of Nuclear Medicine and Endocrinology, 2nd Faculty of Medicine, Charles University and Teaching Hospital Motol, Prague, Czech Republic

    Petr Vlcek

  5. Department of Pediatric Surgery, 2nd Faculty of Medicine, Charles University and Teaching Hospital Motol, Prague, Czech Republic

    Richard Skaba

  6. 3rd Medical Department, Clinical Department of Endocrinology and Metabolism of the First Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic

    Tomas Zelinka

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  1. Eliska Vaclavikova
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Correspondence to Eliska Vaclavikova.

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Vaclavikova, E., Dvorakova, S., Sykorova, V. et al. RET mutation Tyr791Phe: the genetic cause of different diseases derived from neural crest. Endocr 36, 419–424 (2009). https://doi.org/10.1007/s12020-009-9242-7

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  • DOI: https://doi.org/10.1007/s12020-009-9242-7

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