Copelli S B, Lumbroso S, Audran F, Pellizzari E H, Heinrich J J, Cigorraga S B, Sultan C, Chemes H E
Laboratoire d'Hormonologie, H pital Lapeyronie et INSERM U 439 Pathologie des récepteurs nucléaires, Montpellier-France.
Asian J Androl. 1999 Jun;1(1-2):73-7.
To study a 46, XY newborn patient with a phenotype suggestive of an androgen insensitivity syndrome to confirm an anomaly in the AR gene.
Genomic DNA from leukocytes was isolated in order to analyze SRY gene by PCR and sequencing of the eight exons of AR gene. Isolation of human Leydig cell mesenchymal precursors from the testis was performed in order to study testosterone production and response to hCG stimulation in culture.
Surgical exploration disclosed two testes, no Wolffian structures and important Müllerian derivatives. The SRY gene was present in peripheral blood leukocytes. Sequencing of the AR gene evidenced a previously unreported G to T transversion in exon 1 that changed the normal glutamine 153 codon to a stop codon. Interstitial cell cultures produced sizable amounts of testosterone and were responsive to hCG stimulation.
This E153X nonsense point 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 insensitivity syndrome (CAIS).
研究一名46, XY新生儿患者，其表型提示雄激素不敏感综合征，以确认雄激素受体（AR）基因异常。
分离白细胞中的基因组DNA，通过聚合酶链反应（PCR）分析SRY基因，并对AR基因的8个外显子进行测序。从睾丸中分离人睾丸间质细胞间充质前体细胞，以研究睾酮生成及对培养中绒毛膜促性腺激素（hCG）刺激的反应。
手术探查发现两个睾丸，无中肾管结构，有重要的苗勒管衍生物。外周血白细胞中存在SRY基因。AR基因测序显示外显子1中存在一个先前未报道的G到T的颠换，该颠换将正常的谷氨酰胺153密码子变为终止密码子。间质细胞培养产生了大量睾酮，且对hCG刺激有反应。
这种E153X无义点突变在雄激素不敏感综合征病例中此前未被描述，可能导致合成一种短截短的（153个与919个残基）无功能的AR，这可能是完全性雄激素不敏感综合征（CAIS）表型的原因。
