Absence of inactivating mutations and deletions in the DMRT1 and FGF9 genes in a large cohort of 46,XY patients with gonadal dysgenesis

Autor(es)

Machado, Aline Zamboni ^[1] ; da Silva, Thatiana Evilen ^[1] ; Frade Costa, Elaine Maria ^[1] ; dos Santos, Mariza Gerdulo ^[1] ; Nishi, Mirian Yumie ^[1] ; Brito, Vinicius Nahime ^[1] ; Mendonca, Berenice Bilharinho ^[1] ; Domenice, Sorahia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, Lab Hormonios Genet Mol LIM42, Disciplina Endocrinol & Metabol, Hosp Clin, Fac Med, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF MEDICAL GENETICS; v. 55, n. 12, p. 690-694, DEC 2012.
• Citações Web of Science: 4

Resumo

Despite advances in our understanding of the mechanisms involved in sex determination and differentiation, the specific roles of many genes in these processes are not completely understood in humans. Both DMRT1 and FGF9 are among this group of genes. Dmrt1 controls germ cell differentiation, proliferation, migration and pluripotency and Sertoli cell proliferation and differentiation. Fgf9 has been considered a critical factor in early testicular development and germ cell survival in mice. We screened for the presence of DMRT1 and FGF9 mutations in 33 patients with 46,XY gonadal dysgenesis. No deletions in either DMRT1 or FGF9 were identified using the MLPA technique. Eight allelic variants of DMRT1 were identified, and in silico analysis suggested that the novel c.968-15insTTCTCTCT variant and the c.774G>C (rs146975077) variant could have potentially deleterious effects on the DMRT1 protein. Nine previously described FGF9 allelic variants and six different alleles of the 3' UTR microsatellite were identified. However, none of these DMRT1 or FGF9 variants was associated with increased 46,XY gonadal dysgenesis. In conclusion, our study suggests that neither DMRT1 nor FGF9 abnormalities are frequently involved in dysgenetic male gonad development in patients with non-syndromic 46,XY disorder of sex development. (C) 2012 Published by Elsevier Masson SAS. (AU)

• Processo FAPESP: 09/03872-3 - Pesquisa de mutações no gene DMRT1 em pacientes portadores de distúrbios do desenvolvimento sexual 46,XY e 46,XX por anormalidades gonadais
• Beneficiário: Thatiana Evilen da Silva
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 08/55952-8 - Pesquisa de mutações no gene FGF9 e FGFR2 em pacientes portadores de distúrbios do desenvolvimento sexual 46,XY
• Beneficiário: Aline Zamboni Machado
• Modalidade de apoio: Bolsas no Brasil - Mestrado