Yue Fagui, Zhang Hongguo, Xi Qi, Jiang Yuting, Li Leilei, Liu Ruizhi, Wang Ruixue
1Center for Reproductive Medicine, Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun, 130021 China.
2Jilin Engineering Research Center for Reproductive Medicine and Genetics, Jilin University, Changchun, 130021 China.
Mol Cytogenet. 2019 Nov 4;12:44. doi: 10.1186/s13039-019-0456-y. eCollection 2019.
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.
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 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 mutation (c.498G > A, p.R166R), which was not previously reported in -negative XX males.
We proposed that this synonymous 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 -negative XX males. Only after comprehensive cytogenetic and molecular genetic analyses can genetic counseling be offered to 46,XX males.
46,XX男性综合征是一种罕见的疾病，通常会导致不育。本研究旨在通过联合应用细胞遗传学和分子遗传学技术，确定一系列46,XX男性患者中这种疾病的遗传原因。
我们鉴定出8例无精子症的46,XX男性患者，他们在我们中心接受了与不育相关的咨询。他们均表现出正常的男性表型。在这8例46,XX男性患者中的7例（87.5%）中， 基因易位至X染色体短臂末端明显与他们的病情有关，这表明这种易位是46,XX性反转的主要机制，与先前的报道一致。然而，有1例患者出现纯合 突变（c.498G>A，p.R166R），这在 阴性的XX男性中此前未见报道。
我们提出，病例8中的这种同义 突变可能与男性性别决定途径的激活无关，该病例中的男性表型可能受一些未知的遗传或环境因素调控。因此，对于 阴性的XX男性，建议检测关键性别决定基因中与性反转相关的基因变异。只有在进行全面的细胞遗传学和分子遗传学分析后，才能为46,XX男性提供遗传咨询。
