Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Applied Biotechnology Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Mol Genet Genomic Med. 2024 May;12(5):e2448. doi: 10.1002/mgg3.2448.
Infertility is defined as the failure to achieve pregnancy after one year of unprotected intercourse within a marital relationship. Approximately 10%-15% of couples worldwide experience infertility issues, with nearly half of these cases attributed to male factors. Among men with unexplained infertility, genetic mutations have been identified as a potential cause. Studies have indicated that mutations affecting the function of the protein encoded by the ACTL9 gene may play a role in male infertility.
The purpose of this research was to identify mutations in the ACTL9 gene associated with male infertility in a sample of 40 infertile men with unknown causes. Genomic DNA extraction and PCR amplification were carried out on samples from each individual. The genetic material was then analyzed using Sanger sequencing, followed by bioinformatics and segregation analysis to determine the potential effects of the observed variations.
A novel genetic variant, c.376G>A (p.Glu126Lys), was identified in an infertile male individual, representing a previously unreported finding that was validated through segregation analyses. This specific variant induces a change from glutamate to lysine at the amino acid level by replacing the nucleotide G with A in the genomic DNA sequence, consequently impacting the secondary structure and function of the protein.
The conclusive analysis of the procedure indicated that this alteration has the potential to interfere with the process of fertilization, ultimately resulting in the complete failure of fertilization (TFF) and causing male infertility.
不孕不育定义为在婚姻关系中，未采取任何避孕措施的情况下，一年未怀孕。全球约有 10%-15%的夫妇受到不孕不育问题的困扰，其中近一半的病例归因于男性因素。在不明原因不孕不育的男性中，已发现遗传突变是一个潜在的原因。研究表明，影响 ACTL9 基因编码蛋白功能的突变可能与男性不育有关。
本研究旨在鉴定 ACTL9 基因中的突变与 40 名不明原因不孕不育男性个体相关。对每位个体的样本进行基因组 DNA 提取和 PCR 扩增。然后使用 Sanger 测序对遗传物质进行分析，再进行生物信息学和分离分析，以确定观察到的变异的潜在影响。
在一名不孕不育男性个体中发现了一种新的遗传变异，c.376G>A(p.Glu126Lys)，这是一个以前未报道的发现，通过分离分析得到了验证。该特定变异通过将基因组 DNA 序列中的核苷酸 G 替换为 A，导致氨基酸水平上从谷氨酸突变为赖氨酸，从而影响蛋白质的二级结构和功能。
该程序的结论性分析表明，这种改变有可能干扰受精过程，最终导致完全受精失败（TFF）和男性不育。
