RESUMO
We investigated if eight SRY-negative 46,XX true hermaphrodites presented mutations in WNT-4, in blood leukocytes and/or gonadal tissue, as the cause of their disorder. We designed the sequences of the reverse primer of exon 1 and the primers of exons 2-5. Direct sequencing of all five exons demonstrated no mutant alleles in any of the patients. The possibility of the existence of causative mutations in the untranslated regions of WNT-4, or within introns cannot be ruled out.
Assuntos
Transtornos do Desenvolvimento Sexual/genética , Proteínas Proto-Oncogênicas/genética , Pré-Escolar , Transtornos do Desenvolvimento Sexual/sangue , Feminino , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Leucócitos/química , Mutação , Proteínas Wnt , Proteína Wnt4RESUMO
OBJECTIVE: To investigate the presence of mutations in the open reading frame (ORF), as well as on the 5' and 3', flanking regions of the SRY gene in patients with mixed gonadal dysgenesis (MGD) or with Turner syndrome (TS) and Y mosaicism. STUDY DESIGN: We studied 13 patients with MGD and three patients with TS and Y mosaicism. DNA was isolated from blood leukocytes for subsequent polymerase chain reaction (PCR) and direct sequencing were performed in the ORF, as well as from the 5' and 3' flanking regions of the SRY gene. RESULTS: No mutations were present in any of the patients studied. CONCLUSION: The absence of mutations in these regions indicated that mutations were an unlikely cause of MGD or TS with Y mosaicism and suggested that there are others genes playing an important role in sex development.
Assuntos
Cromossomos Humanos Y/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Disgenesia Gonadal Mista/genética , Mosaicismo/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Síndrome de Turner/genética , Adolescente , Adulto , Criança , Pré-Escolar , DNA/sangue , Humanos , Lactente , Leucócitos/química , Masculino , Fases de Leitura Aberta/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Proteína da Região Y Determinante do SexoRESUMO
True hermaphroditism (TH) is an unusual form of sex reversal, characterized by the development of testicular and ovarian tissue in the same subject. Approximately 60% of the patients have a 46,XX karyotype, 33% are mosaics with a second cell line containing a Y chromosome, while the remaining 7% are 46,XY. Molecular analyses have demonstrated that SRY is present in only 10% of TH with a 46,XX karyotype; therefore, in the remaining 90%, mutations at unknown X-linked or autosomal sex determining loci have been proposed as factors responsible for testicular development. True hermaphroditism presents considerable genetic heterogeneity with several molecular anomalies leading to the dual gonadal development as SRY point mutations or SRY hidden gonadal mosaicism. In order to identify genetic defects associated with subjects with the disease, we performed molecular analyses of the SRY gene in DNA from blood leukocytes and gonadal tissue in 12 true hermaphrodites with different karyotypes. Our results using PCR and FISH analyses reveal the presence of hidden mosaicism for SRY or other Y sequences in some patients with XX true hermaphroditism and confirms that mosaicism for SRY limited to the gonads is an alternative mechanism for testicular development in 46,XX true hermaphrodites.