Zhang Wei, Zhou Xueya, Liu Liyang, Zhu Ying, Liu Chunmei, Pan Hong, Xing Qiong, Wang Jing, Wang Xi, Zhang Xuegong, Cao Yunxia, Wang Binbin
Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Graduate School, Peking Union Medical College, Beijing, China.
Oncotarget. 2017 Jan 31;8(5):8785-8790. doi: 10.18632/oncotarget.14455.
Congenital absence of the uterus and vagina (CAUV) is the most extreme female Müllerian duct abnormality. Several researches proposed that genetic factors contributed to this disorder, whereas the precise genetic mechanism is far from full elucidation. Here, utilizing whole-exome sequencing (WES), we identified one novel missense mutation in LHX1 (NM_005568: c.G1108A, p.A370T) in one of ten unrelated patients diagnosed with CAUV. This mutation was absent from public databases and our internal database. Through the luciferase reporter analysis, we found that the mutation could change the transcriptional activity of LHX1 and its effect on the regulation of the downstream target gene GSC, which might be associated with urogenital system development. In short, we concluded that the LHX1 may be a pathogenic gene of CAUV. Our results demonstrate the power of whole exome sequencing and gene prioritization approach as diagnostic tools in clinical practice that help make genetic diagnosis of CAUV.
先天性子宫和阴道缺失（CAUV）是最严重的女性苗勒管异常。多项研究表明遗传因素导致了这种疾病，然而其确切的遗传机制远未完全阐明。在此，我们利用全外显子组测序（WES），在10名被诊断为CAUV的无血缘关系患者中的1例中，鉴定出LHX1基因（NM_005568: c.G1108A, p.A370T）的一个新的错义突变。该突变在公共数据库和我们的内部数据库中均未出现。通过荧光素酶报告基因分析，我们发现该突变可改变LHX1的转录活性及其对下游靶基因GSC调控的影响，这可能与泌尿生殖系统发育有关。简而言之，我们得出结论，LHX1可能是CAUV的致病基因。我们的结果证明了全外显子组测序和基因优先级排序方法作为临床实践中的诊断工具，有助于对CAUV进行基因诊断的能力。
