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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

RET haplotype, not linked to the C620R activating mutation, associated with Hirschsprung disease in a novel MEN2 family

Texto completo
Autor(es):
Quedas, Elisangela P. S. [1] ; Longuini, Viviane C. [1] ; Sekiya, Tomoko [1] ; Coutinho, Flavia L. [1] ; Toledo, Sergio P. A. [1] ; Tannuri, Uenis [2, 3] ; Toledo, Rodrigo A. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med, Endocrine Genet Unit LIM 25, Div Endocrinol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Div Pediat Surg, Sao Paulo - Brazil
[3] Lab Pediat Surg LIM 30, Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo de Revisão
Fonte: Clinics; v. 67, n. 1, p. 57-61, 2012.
Citações Web of Science: 3
Resumo

Hirschsprung disease is a congenital form of aganglionic megacolon that results from cristopathy. Hirschsprung disease usually occurs as a sporadic disease, although it may be associated with several inherited conditions, such as multiple endocrine neoplasia type 2. The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease. The prevalence of Hirschsprung disease in multiple endocrine neoplasia type 2 cases was recently determined to be 7.5% and the co-occurrence of Hirschsprung disease and multiple endocrine neoplasia type 2 has been reported in at least 22 families so far. It was initially thought that Hirschsprung disease could be due to disturbances in apoptosis or due to a tendency of the mutated RET receptor to be retained in the Golgi apparatus. Presently, there is strong evidence favoring the hypothesis that specific inactivating haplotypes play a key role in the fetal development of congenital megacolon/Hirschsprung disease. In the present study, we report the genetic findings in a novel family with multiple endocrine neoplasia type 2: a specific RET haplotype was documented in patients with Hirschsprung disease associated with medullary thyroid carcinoma, but it was absent in patients with only medullary thyroid carcinoma. Despite the limited number of cases, the present data favor the hypothesis that specific haplotypes not linked to RET germline mutations are the genetic causes of Hirschsprung disease. (AU)

Processo FAPESP: 09/15386-6 - Análise dos genes CDKN1A, CDKN1B, CDKN2B e CDKN2C, nas Neoplasias Endócrinas Múltiplas tipo 1 e 2
Beneficiário:Rodrigo de Almeida Toledo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado