Aim: To study a 46, XY newborn patient with a phenotype suggestive of an androgen insensitivity syndrome toconfirn an anomaly in the AR gene. Methods: Genomic DNA from leukocytes was isolated in order to analyze SRYge...Aim: To study a 46, XY newborn patient with a phenotype suggestive of an androgen insensitivity syndrome toconfirn an anomaly in the AR gene. Methods: Genomic DNA from leukocytes was isolated in order to analyze SRYgene by PCR and sequencing of the eight exons of AR gene. Isolation of human Leydig cell mesenchymal precursorsfrom the testis was performed in order to study testosterone production and response to hCG stimulation in culture.Results: Surgical exploration disclosed two testes, no Wolffian structures and important Mullerian derivatives. TheSRY gene was present in peripheral blood leukocytes. Sequencing of the AR gene evidenced a previously unreported Gto T transversion in exon 1 that changed the normal glutamine 153 codon to a stop codon. Interstitial cell culturesproduced sizable amounts of testosterone and were responsive to hCG stimulation. Conclusion: This E153X nonsensepoint mutation has not been described previously in cases of AIS, and could lead to the synthesis of a short truncated(153 vs 919 residues) non functional AR probably responsible for the phenotype of complete androgen insensitivitysyndrome (CAIS).展开更多
基金Supported by grants PMT-PICT 0090 from CONICET, and PICT 0450 from ANPCyT, Argentina, and Institu National de le Sante et de la Recherche Medicale, INSERM, France
文摘Aim: To study a 46, XY newborn patient with a phenotype suggestive of an androgen insensitivity syndrome toconfirn an anomaly in the AR gene. Methods: Genomic DNA from leukocytes was isolated in order to analyze SRYgene by PCR and sequencing of the eight exons of AR gene. Isolation of human Leydig cell mesenchymal precursorsfrom the testis was performed in order to study testosterone production and response to hCG stimulation in culture.Results: Surgical exploration disclosed two testes, no Wolffian structures and important Mullerian derivatives. TheSRY gene was present in peripheral blood leukocytes. Sequencing of the AR gene evidenced a previously unreported Gto T transversion in exon 1 that changed the normal glutamine 153 codon to a stop codon. Interstitial cell culturesproduced sizable amounts of testosterone and were responsive to hCG stimulation. Conclusion: This E153X nonsensepoint mutation has not been described previously in cases of AIS, and could lead to the synthesis of a short truncated(153 vs 919 residues) non functional AR probably responsible for the phenotype of complete androgen insensitivitysyndrome (CAIS).
