A novel homozygous missense mutation of PMFBP1 causes acephalic spermatozoa syndrome

J Assist Reprod Genet. 2021 Apr;38(4):949-955. doi: 10.1007/s10815-021-02075-7. Epub 2021 Jan 23.

Abstract

Purpose: To identify the pathogenic mutation in PMFBP1 leading to acephalic spermatozoa syndrome.

Methods: Sanger sequencing was used to screen for mutations in the known pathogenic genes SUN5 and PMFBP1 in a patient with acephalic spermatozoa syndrome. Western blotting and immunofluorescence were used to detect the expression and localization of PMFBP1 in sperm. At the same time, a PMFBP1 mutant was constructed, and the expression level of PMFBP1 protein was further verified by in vitro experiments.

Results: We identified a novel homozygous PMFBP1 missense mutation, c.301A>C (p.T101P), in an infertile male from a consanguineous family. Our results showed that the expression of PMFBP1 mutant protein was decreased obviously in sperm of the patient.

Conclusion: Our results showed that the novel homozygous missense mutation of PMFBP1 may be a cause of acephalic spermatozoa syndrome, which provided a basis for genetic counseling for the patient.

Keywords: Acephalic spermatozoa syndrome; Missense mutation; PMFBP1; Sanger sequencing.

MeSH terms

  • Exome Sequencing
  • Homozygote
  • Humans
  • Infertility, Male / genetics*
  • Infertility, Male / pathology
  • Male
  • Membrane Proteins / genetics*
  • Mutation / genetics
  • Mutation, Missense / genetics
  • Pedigree
  • Spermatozoa / growth & development
  • Spermatozoa / pathology
  • Teratozoospermia / genetics*
  • Teratozoospermia / pathology

Substances

  • Membrane Proteins