Comprehensive analysis of RET gene should be performed in patients with multiple endocrine neoplasia type 2 (MEN 2) syndrome and no apparent genotype- phenotype correlation: An appraisal of p.Y791F and p.C634Y RET mutations in five unrelated Brazilian families

Comprehensive analysis of RET gene should be performed in patients with multiple endocrine neoplasia type 2 (MEN 2) syndrome and no apparent genotype- phenotype correlation: An appraisal of p.Y791F and p.C634Y RET mutations in five unrelated Brazilian families

Author Valente, F. O. F. Autor UNIFESP Google Scholar
Dias-da-Silva, Magnus Régios Autor UNIFESP Google Scholar
Camacho, C. P. Autor UNIFESP Google Scholar
Kunii, I. S. Autor UNIFESP Google Scholar
Bastos, A. U. Autor UNIFESP Google Scholar
Fonseca, C. C. N. da Autor UNIFESP Google Scholar
Simiao, H. P. C. Autor UNIFESP Google Scholar
Tamanaha, R. Autor UNIFESP Google Scholar
Maciel, R. M. B. Autor UNIFESP Google Scholar
Cerutti, J. M. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Background: We previously identified a four-generation family with medullary thyroid cancer (MTC) and a germline p.Y791F RET mutation whose cancer lacked a strong genotype-phenotype correlation. the entire gene coding region of the RET gene should be sequenced when genotype-phenotype discrepancies are observed in patients with multiple endocrine neoplasia type 2 (MEN 2), even if a RET hotspot mutation has been identified. Methods: A new genetic test was performed in the index case of this family with the p.Y791F RET germline mutation. the entire coding region of the RET gene was investigated by direct sequencing of PCR products. Once a mutation was identified, the target exon was sequenced in all at-risk relatives. Results: An additional p.C634Y germline mutation in the RET gene was identified in the reported family. the double mutation occurred in cis and segregated with the phenotype. Through the Brazilian Genetic Screening Program developed at our institution, we additionally report the combination of these two mutations (p.C634Y/p. Y791F) in the RET gene in four other unrelated families. the overall penetrance of MTC and pheochromocytoma in patients with the p.C634Y/p.Y791F mutations was 79% and 13%, respectively. Conclusion: Our data emphasises that a comprehensive analysis of the RET gene may reveal multiple germline mutations in MEN 2 patients who exhibit an atypical clinical course of the disease. (C) 2013, Editrice Kurtis
Keywords MEN 2A
RET
p.C634Y
p.Y791F
medullary thyroid carcinoma
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 06/54922-2
FAPESP: 09/11257-7
Date 2013-12-01
Published in Journal of Endocrinological Investigation. New York: Springer, v. 36, n. 11, p. 975-981, 2013.
ISSN 1720-8386 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 975-981
Origin http://link.springer.com/article/10.3275%2F8997
Access rights Closed access
Type Article
Web of Science ID WOS:000335151000010
URI http://repositorio.unifesp.br/handle/11600/37071

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