Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed patients

Autor(es)

S. Domenice ^[1] ; R.V. Corrêa ^[2] ; E.M.F. Costa ^[3] ; M.Y. Nishi ^[4] ; E. Vilain ^[5] ; I.J.P. Arnhold ^[6] ; B.B. Mendonca ^[7]

Afiliação do(s) autor(es)

^[1] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[2] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[3] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[4] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[5] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[6] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[7] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 37, n. 1, p. 145-150, 2004-01-00.

Resumo

In most mammals, male development is triggered by the transient expression of the SRY gene, which initiates a cascade of gene interactions ultimately leading to the formation of a testis from the indifferent fetal gonad. Mutation studies have identified several genes essential for early gonadal development. We report here a molecular study of the SRY, DAX1, SF1 and WNT4 genes, mainly involved in sexual determination, in Brazilian 46,XX and 46,XY sex-reversed patients. The group of 46,XX sex-reversed patients consisted of thirteen 46,XX true hermaphrodites and four 46,XX males, and was examined for the presence of the SRY gene and for the loss of function (inactivating mutations and deletions) of DAX1 and WNT4 genes. In the second group consisting of thirty-three 46,XY sex-reversed patients we investigated the presence of inactivating mutations in the SRY and SF1 genes as well as the overexpression (duplication) of the DAX1 and WNT4 genes. The SRY gene was present in two 46,XX male patients and in none of the true hermaphrodites. Only one mutation, located outside homeobox domain of the 5' region of the HMG box of SRY (S18N), was identified in a patient with 46,XY sex reversal. A novel 8-bp microdeletion of the SF1 gene was identified in a 46,XY sex-reversed patient without adrenal insufficiency. The dosage of DAX1 and WNT4 was normal in the sex-reversed patients studied. We conclude that these genes are rarely involved in the etiology of male gonadal development in sex-reversed patients, a fact suggesting the presence of other genes in the sex determination cascade. (AU)

• Processo FAPESP: 00/01737-7 - Analise molecular dos genes dax-1 e sf1 em pacientes portadores de disturbios da determinacao gonadal.
• Beneficiário: Sorahia Domenice
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 00/06678-9 - Estudo dos genes DAX-1 e SF-1 em pacientes portadores de distúrbios da determinação gonadal
• Beneficiário: Rafaela Vieira Correa
• Modalidade de apoio: Bolsas no Brasil - Doutorado