Background 46,XX male syndrome is a rare disorder that usually causes infertility. This study was established to identify the genetic causes of this condition in a series of 46,XX males through the combined application of cytogenetic and molecular genetic techniques. Case presentation We identified eight azoospermic 46,XX males who underwent infertility-related consultations at our center. They all presented normal male phenotypes. In seven of the eight 46,XX males (87.5%), translocation of the SRY gene to the terminal short arm of the X chromosome was clearly involved in their condition, which illustrated that this translocation is the main mechanism of 46,XX sex reversal, in line with previous reports. However, one patient presented a homozygous DAX1 mutation (c.498G > A, p.R166R), which was not previously reported in SRY-negative XX males. Conclusions We proposed that this synonymous DAX1 mutation in case 8 might not be associated with the activation of the male sex-determining pathway, and the male phenotype in this case might be regulated by some unidentified genetic or environmental factors. Hence, the detection of genetic variations associated with sex reversal in critical sex-determining genes should be recommended for SRY-negative XX males. Only after comprehensive cytogenetic and molecular genetic analyses can genetic counseling be offered to 46,XX males.

中文翻译：

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分子细胞遗传学分析与遗传咨询：8例46，XX男性病例报告及文献复习。

背景 46,XX 男性综合征是一种罕见的疾病，通常会导致不育。本研究旨在通过细胞遗传学和分子遗传学技术的联合应用，在一系列 46,XX 男性中确定这种情况的遗传原因。病例介绍 我们确定了八名无精子症的 46,XX 男性，他们在我们的中心接受了与不孕症相关的咨询。他们都表现出正常的男性表型。8名46,XX男性中有7名（87.5%）SRY基因易位至X染色体末端短臂明显参与其病情，说明该易位是46,XX性别逆转的主要机制，与之前的报道一致。然而，一名患者出现了纯合 DAX1 突变（c.498G > A，p.R166R），这在 SRY 阴性 XX 男性中以前没有报道过。结论 我们提出，病例 8 中的这种同义 DAX1 突变可能与男性性别决定途径的激活无关，并且该病例中的男性表型可能受一些未知的遗传或环境因素的调节。因此，对于 SRY 阴性 XX 男性，应建议检测与关键性别决定基因中的性别逆转相关的遗传变异。只有经过全面的细胞遗传学和分子遗传学分析，才能为 46,XX 名男性提供遗传咨询。对于 SRY 阴性 XX 男性，应推荐检测与关键性别决定基因中的性别逆转相关的遗传变异。只有经过全面的细胞遗传学和分子遗传学分析，才能为 46,XX 名男性提供遗传咨询。对于 SRY 阴性 XX 男性，应推荐检测与关键性别决定基因中的性别逆转相关的遗传变异。只有经过全面的细胞遗传学和分子遗传学分析，才能为 46,XX 名男性提供遗传咨询。