Novel mutations of PMFBP1 in a man with acephalic spermatozoa defects

Background: Acephalic spermatozoa (AS) is a serious but rare reproductive genetic disorder that causes infertility in men. To date, only a few genes associated with AS defects have been identified, including the polyamine modulated factor 1 binding protein 1 (PMFBP1) gene. Consistent with this, PMFBP1 localizes to the head-neck connection, which bridges the implantation fossa and basal body. Methods: A male patient was diagnosed as having an AS defect. Blood samples from all family members and a sample of the patient's semen were collected to determine the genetic causes of his infertility. Results: Compound heterozygote mutation in the PMFBP1 gene, which is associated with AS defects in the present case: two loss-of-function mutations, with one a nonsense mutation c.361C > T p.G1n121Ter, and another a splice donor mutation c.414 +1G> T. The current study, together with previous studies, suggests that the nonsense mutation is responsible for a truncated PMFBPI protein during its formation; a splice donor mutation c.414 +1G > T might lead to new open reading frames, from which the dysfunction of an abnormal PMFBP1 protein might be predicted. Additionally, the expression of outer dense fiber 1 (ODF1) and ODF2 proteins has been experimentally shown to be regulated by the truncated PMFBP1 protein. Conclusion: We herein present a case with AS defects associated with heterozygote mutations of PMFBP1, which have been shown to be rare and pathogenic; the association with an AS defect is a monogenic disorder with a recessive inherited pattern in the patient's family.