Ragitha T S, Sunish K S, Gilvaz Sareena, Daniel Saley, Varghese P R, Raj Soumya, Francis Jijo, Suresh Kumar R
Maharaja's College (Government- Autonomous), Ernakulam, Kerala, India; Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India.
Maharaja's College (Government- Autonomous), Ernakulam, Kerala, India.
Gene. 2023 Apr 20;861:147236. doi: 10.1016/j.gene.2023.147236. Epub 2023 Feb 2.
Developmental disruption of the Mullerian duct and gonads in females leads to Mullerian agenesis and gonadal dysgenesis, respectively. These two structural abnormalities are coming under the 46,XX DSD (Disorders of Sexual Development) classification, the majority of cases the aetiology remains elusive. Without the SRY gene, WNT4 plays a key role in female reproductive structure development. Since there are no studies that explored the involvement of the WNT4 gene in Indian 46,XX DSD patients, we analysed the role of WNT4 in Indian 46,XX DSD patients with Mullerian agenesis and/or Gonadal dysgenesis. In our study, we recruited 103 adolescent girls with primary amenorrhea. After the cytogenetic and SRY gene analysis, we included thirty-two 46,XX DSD patients with Mullerian agenesis and/or gonadal dysgenesis for WNT4 gene mutation analysis. PCR sequencing was performed for all the coding exons of the WNT4 gene. Bioinformatic tools like Mutation Taster, Human Splicing Finder, and miRDB were used. We observed single nucleotide variations in three patients. One patient showed a known synonymous polymorphism (c.861C > T; p.G287G, rs544988174). miRDB data revealed the absence of microRNA regulatory sites in this region. The other two cases carried a nucleotide substitution in intronic regions and did not affect the normal splicing mechanism. In conclusion, we could not find any indication about WNT4 involvement in the disease condition. In the future, WNT4 promoter analysis in these patients and molecular characterization of the WNT4 coding and promoter region in more patients are needed to link WNT4 variants with these structural abnormalities.
女性苗勒管和性腺的发育中断分别导致苗勒管发育不全和性腺发育不全。这两种结构异常属于46,XX性发育障碍（DSD）分类，大多数病例的病因仍然不明。由于没有SRY基因，WNT4在女性生殖结构发育中起关键作用。鉴于尚无研究探讨WNT4基因在印度46,XX DSD患者中的作用，我们分析了WNT4在患有苗勒管发育不全和/或性腺发育不全的印度46,XX DSD患者中的作用。在我们的研究中，我们招募了103名原发性闭经的青春期女孩。经过细胞遗传学和SRY基因分析后，我们纳入了32名患有苗勒管发育不全和/或性腺发育不全的46,XX DSD患者进行WNT4基因突变分析。对WNT4基因的所有编码外显子进行了PCR测序。使用了Mutation Taster、Human Splicing Finder和miRDB等生物信息学工具。我们在三名患者中观察到单核苷酸变异。一名患者显示出已知的同义多态性（c.861C>T；p.G287G，rs544988174）。miRDB数据显示该区域不存在微小RNA调控位点。另外两例在内含子区域发生了核苷酸替换，并未影响正常的剪接机制。总之，我们没有发现任何表明WNT4参与该疾病状况的迹象。未来，需要对这些患者进行WNT4启动子分析，并对更多患者的WNT4编码区和启动子区域进行分子特征分析，以将WNT4变异与这些结构异常联系起来。
