Abstract：
Asthenoteratospermia is a significant cause of male infertility. FAM71D (Family with sequence similarity 71, member D), as a novel protein exclusively expressed in the testis, has been found to be associated with sperm motility. However, the association of FAM71D mutation with male infertility has yet to be examined. Here, we conducted whole-exome sequencing and identified a homozygous missense mutation c.440G > A (p. Arg147Gln) of FAM71D in an asthenoteratospermia-affected man from a consanguineous family. The FAM71D variant is extremely rare in human population genome databases and predicted to be deleterious by multiple bioinformatics tools. Semen analysis indicated decreased sperm motility and obvious morphological abnormalities in sperm cells from the FAM71D-deficient man. Immunofluorescence assays revealed that the identified FAM71D mutation had an important influence on the assembly of sperm structure-related proteins. Furthermore, intra-cytoplasmic sperm injection (ICSI) treatment performed on the infertile man with FAM71D variant achieved a satisfactory outcome. Overall, our study identified FAM71D as a novel causative gene for male infertility with asthenoteratospermia, for which ICSI treatment may be suggested to acquire good prognosis. All these findings will provide effective guidance for genetic counselling and assisted reproduction treatments of asthenoteratospermia-affected subjects.
摘要：
弱精子症是男性不育的重要原因。FAM71D（具有序列相似性的家族71，成员D），作为一种仅在睾丸中表达的新型蛋白质，已经发现与精子活力有关。然而,FAM71D突变与男性不育的相关性尚待研究.这里,我们进行了全外显子组测序，鉴定出一个纯合错义突变c.440G>A（p。来自近亲家庭的受弱精子症影响的FAM71D的Arg147Gln）。FAM71D变体在人群基因组数据库中极为罕见，并且被多种生物信息学工具预测是有害的。精液分析表明，FAM71D缺陷型男性的精子活力下降，精子细胞形态异常明显。免疫荧光分析显示，鉴定的FAM71D突变对精子结构相关蛋白的组装有重要影响。此外，对FAM71D变异的不育男性进行的胞浆内精子注射(ICSI)治疗取得了满意的结果.总的来说,我们的研究确定FAM71D是男性不育伴弱精子症的新致病基因，可能建议ICSI治疗以获得良好预后。所有这些发现将为受弱精子症影响的受试者的遗传咨询和辅助生殖治疗提供有效指导。
