Abnormal gonadal differentiation in two subjects with ambiguous genitalia, Mullerian structures, and normally developed testes: evidence for a defect in gonadal ridge development.
Abnormal gonadal differentiation in two subjects with ambiguous genitalia, Mullerian structures, and normally developed testes: evidence for a defect in gonadal ridge development.
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两名生殖器、苗勒管结构和睾丸发育正常的受试者的性腺分化异常：性腺嵴发育缺陷的证据。
DOI：
10.1007/bf02267076
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发表时间：
1996
期刊：
影响因子：
5.3
通讯作者：
Berkovitz,GD
中科院分区：
文献类型：
--
作者：
Fuqua,JS;Sher,ES;Perlman,EJ;Urban,MD;Ghahremani,M;Pelletier,J;Migeon,CJ;Brown,TR;Berkovitz,GD
在一组性别分化异常的患者中，我们发现两名受试者的染色体核型为 46,XY，生殖器不明确，苗勒管结构发育良好，但睾丸外观正常。不明确的生殖器和持续的苗勒管结构的存在意味着间质细胞和支持细胞功能障碍，因此，性腺发育不全。然而，正常的睾丸组织学表明，潜在的异常不是睾丸测定本身的缺陷，而是性腺嵴和睾丸发育时间的异常。两名受试者中的一名获得了基因组 DNA。 SRY基因序列正常。由于部分雄激素不敏感的罕见患者可能具有相似的表型，因此通过变性梯度凝胶电泳（DGGE）评估AR基因，结果显示为正常。一些携带 WT1 基因突变或 9 号染色体远端短臂缺失的受试者可能具有相似的表型。 WT1基因经单链构象多态性（SSCP）分析显示正常。此外，远端 9p 的多态性标记的杂合性没有丢失。苗勒氏管抑制物质（MIS）基因也通过 SSCP 研究正常。尽管两名受试者缺陷的确切机制尚不清楚，但可能是由于与性腺嵴发育时间有关的一个或多个基因的异常所致。
Among a group of patients with abnormal sexual differentiation, we have identified two subjects who had a 46,XY karyotype, ambiguous genitalia, and well-developed Müllerian structures, but normal appearing testes. The presence of ambiguous genitalia and persistent Müllerian structures implied both Leydig cell and Sertoli cell dysfunction, hence, gonadal dysgenesis. However, the normal testicular histology suggested that the underlying abnormality was not a defect in testis determination itself but an abnormality in timing of gonadal ridge and testis development. In one of the two subjects genomic DNA was available. The sequence of the SRY gene was normal. Because rare patients with partial androgen insensitivity may have a similar phenotype, the AR gene was evaluated by denaturing gradient gel electrophoresis (DGGE) and was normal. Some subjects with mutation of the WT1 gene or with deletion of the distal short arm of chromosome 9 may have similar phenotypes. The WT1 gene was studied by single-strand conformation polymorphism (SSCP) analysis and was normal. In addition, there was no loss of heterozygosity of polymorphic markers in distal 9p. The gene for Müllerian inhibiting substance (MIS) was also studied by SSCP and was normal. Although the exact mechanism for the defect in the two subjects is unknown, it may be due to an abnormality in a gene or genes involved in the timing of gonadal ridge development.