A Novel Double RET E768D/L790F Mutation Associated with a MEN2B-Like Phenotype.
Thyroid
; 31(2): 327-329, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-32546069
ABSTRACT
Background:
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder caused by mutations in the RET proto-oncogene. MEN2 is classified into two subtypes, MEN 2A and 2B. MEN2B is characterized by early-onset and aggressive medullary thyroid carcinoma (MTC), pheochromocytoma, and characteristic physical features. PatientFindings:
We present a 39-year-old male with early-onset metastatic MTC diagnosed at the age of 13 years and physical features typical for MEN2B such as marfanoid habitus, mucosal neuromas, and thickened eyelids. The patient has two first-degree relatives (mother and maternal uncle) with MTC and pheochromocytoma. The mother has similar facial features. RET sequencing revealed a novel tandem RET E768D/L790F germline mutation in exon 13. The patient's mother has the same RET variant. For functional in vitro characterization, wild-type RET, RET E768D, RET L790F, the double RET E768D/L790F mutant, and RET M918T were expressed in HEK293 cells. The novel double RET E768D/L790F mutant increased ligand-independent RET phosphorylation, activation of the mitogen-activated protein kinase (MAPK)-pathway, and colony formation similar to the classical MEN2B RET M918T mutation.Summary:
In this male patient with a MEN2B-like phenotype, we identified a novel double RET germline mutation, E768D/L790F. Functional characterization of the double mutant shows similar transforming capacity as RET M918T.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Tiroides
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Biomarcadores de Tumor
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Carcinoma Neuroendocrino
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Neoplasia Endocrina Múltiple Tipo 2b
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Proteínas Proto-Oncogénicas c-ret
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Mutación
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Thyroid
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania