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Novel mutations of PMFBP1 in a man with acephalic spermatozoa defects
Hua Nie1,2,3, Yunge Tang1,2,3, Xiaoyu Zhang4
1NHC Key Laboratory of Male Reproduction and Genetics, Guangzhou, China.
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.Gln121Ter, 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 PMFBP1 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.
Insights
Acephalic spermatozoa (AS), a rare cause of male infertility, is linked to mutations in the PMFBP1 gene. This study identifies compound heterozygote mutations in PMFBP1, confirming its role in AS pathogenesis.
Area of Science:
- Genetics
- Reproductive Medicine
- Molecular Biology
Background:
- Acephalic spermatozoa (AS) is a rare genetic disorder causing male infertility.
- The polyamine modulated factor 1 binding protein 1 (PMFBP1) gene is implicated in AS.
- PMFBP1's localization at the sperm head-neck connection is critical.
Purpose of the Study:
- To investigate the genetic basis of AS in a male patient.
- To identify mutations in the PMFBP1 gene associated with AS.
- To understand the inheritance pattern of AS within the family.
Main Methods:
- Genetic analysis of blood samples from family members.
- Semen analysis of the affected patient.
- Identification of mutations in the PMFBP1 gene.
Main Results:
- The patient presented with compound heterozygote mutations in the PMFBP1 gene.
- Identified mutations include a nonsense mutation (c.361C>T p.Gln121Ter) and a splice donor mutation (c.414+1G>T).
- These mutations lead to a truncated or abnormal PMFBP1 protein, affecting ODF1 and ODF2 expression.
Conclusions:
- PMFBP1 mutations are rare, pathogenic, and associated with AS.
- AS in this case follows a monogenic, recessive inheritance pattern.
- This study reinforces PMFBP1's role in male infertility due to AS.
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