PDF(Pubmed)
Abstract：
In this study, we investigated the role of a newly identified homozygous variant (c.1245 + 6T > C) in the CFAP61 gene in the development of multiple morphologically abnormal flagella (MMAF) in an infertile patient. Using exome sequencing, we identified this variant, which led to exon 12 skipping and the production of a truncated CFAP61 protein. Transmission electron microscopy analysis of the patient\'s spermatozoa revealed various flagellar abnormalities, including defective nuclear chromatin condensation, axoneme disorganization, and mitochondria embedded in residual cytoplasmic droplets. Despite a fertilization rate of 83.3% through ICSI, there was no successful pregnancy due to poor embryo quality.Our findings suggest a link between the identified CFAP61 variant and MMAF, indicating potential disruption in radial spokes\' assembly or function crucial for normal ciliary motility. Furthermore, nearly half of the observed sperm heads displayed chromatin condensation defects, possibly contributing to the low blastulation rate. This case underscores the significance of genetic counseling and testing, particularly for couples dealing with infertility and MMAF. Early identification of such genetic variants can guide appropriate interventions and improve reproductive outcomes.
摘要：
在这项研究中,我们研究了CFAP61基因中一个新发现的纯合变异体(c.1245+6T>C)在不育患者多个形态异常鞭毛(MMAF)发育中的作用.使用外显子组测序，我们确定了这个变体，这导致外显子12跳跃和截短的CFAP61蛋白的产生。患者精子的透射电镜分析显示各种鞭毛异常，包括有缺陷的核染色质凝聚，轴突混乱，和线粒体包埋在残留的细胞质液滴中。尽管通过ICSI的受精率为83.3%，由于胚胎质量差，没有成功怀孕。我们的研究结果表明，确定的CFAP61变体和MMAF之间存在联系，表明对正常纤毛运动至关重要的径向辐条组装或功能的潜在破坏。此外，近一半的精子头显示染色质凝结缺陷，可能导致低囊胚率。这个案例强调了遗传咨询和检测的重要性，特别是对于处理不孕症和MMAF的夫妇。早期识别这种遗传变异可以指导适当的干预措施并改善生殖结果。
