• PMID: 30298696
• Gene Name: PMFBP1
• Condition: Acephalic spermatozoa
• Association: Associated
• Mutation: c.2561_2562del:p.K854Rfs*5 and c.327 T > A:p.Y109X
• Population size: 2
• Population details: 2 with acephalic spermatozoa
• Age: 33 yrs, 31 yrs
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

Biallelic mutations in PMFBP1 cause acephalic spermatozoa

Sha YW, Wang X, Xu X, Ding L, Liu WS, Li P, Su ZY, Chen J, Mei LB, Zheng LK, Wang HL, Kong SB, You M, Wu JF.

The majority of men with defects in spermatogenesis remain undiagnosed. Acephalic spermatozoa is one of the diseases causing primary infertility. However, the causes underlying over half of affected cases remain unclear. Here, we report by whole-exome sequencing the identification of homozygous and compound heterozygous truncating mutations in PMFBP1 of two unrelated individuals with acephalic spermatozoa. PMFBP1 was highly and specifically expressed in human and mouse testis. Furthermore, immunofluorescence staining in sperm from a normal control showed that PMFBP1 localizes to the head-flagella junction region, and the absence of PMFBP1 was confirmed in patients harboring PMFBP1 mutations. In addition, we generated Pmfbp1 knock-out (KO) mice, which we found recapitulate the acephalic sperm phenotype. Label-free quantitative proteomic analysis of testicular sperm from Pmfbp1 KO and control mice showed 124 and 35 proteins, respectively, increased or decreased in sperm from KO mice compared to that found in control mice. Gene ontology analysis indicates that the biological process of Golgi vesicle transport was the most highly enriched in differentially expressed proteins, indicating process defects related to Golgi complex function may disturb formation of the head-neck junction. Collectively, our data indicate that PMFBP1 is necessary for sperm morphology in both humans and mice, and that biallelic truncating mutations in PMFBP1 cause acephalic spermatozoa. CI - © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Sha, Yan-Wei AU - Sha YW AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Wang, Xiong AU - Wang X AD - Reproductive Medicine Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. FAU - Xu, Xiaohui AU - Xu X AD - School of Pharmaceutical Sciences, Xiamen University, Xiamen, China. FAU - Ding, Lu AU - Ding L AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Liu, Wen-Sheng AU - Liu WS AD - School of Pharmaceutical Sciences, Xiamen University, Xiamen, China. FAU - Li, Ping AU - Li P AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Su, Zhi-Ying AU - Su ZY AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Chen, Jing AU - Chen J AUID- ORCID: 0000-0002-2451-5928 AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Mei, Li-Bin AU - Mei LB AD - Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Zheng, Liang-Kai AU - Zheng LK AD - Department of Pathology, Xiamen Maternity and Child Care Hospital, Xiamen, China. FAU - Wang, Hai-Long AU - Wang HL AD - School of Medicine, Xiamen University, Xiamen, China. FAU - Kong, Shuang-Bo AU - Kong SB AD - School of Medicine, Xiamen University, Xiamen, China. FAU - You, Min AU - You M AD - School of Public Health, Xiamen University, Xiamen, China.