Biallelic SUN5 Mutations Cause Autosomal-Recessive Acephalic Spermatozoa Syndrome

Am J Hum Genet. 2016 Oct 6;99(4):942-949. doi: 10.1016/j.ajhg.2016.08.004. Epub 2016 Sep 15.


Acephalic spermatozoa syndrome is a rare and severe form of teratozoospermia characterized by a predominance of headless spermatozoa in the ejaculate. Family clustering and consanguinity suggest a genetic origin; however, causative mutations have yet to be identified. We performed whole-exome sequencing in two unrelated infertile men and subsequent variant filtering identified one homozygous (c.824C>T [p.Thr275Met]) and one compound heterozygous (c.1006C>T [p.Arg356Cys] and c.485T>A [p.Met162Lys]) SUN5 (also named TSARG4) variants. Sanger sequencing of SUN5 in 15 additional unrelated infertile men revealed four compound heterozygous (c.381delA [p.Val128Serfs7] and c.824C>T [p.Thr275Met]; c.381delA [p.Val128Serfs7] and c.781G>A [p.Val261Met]; c.216G>A [p.Trp72] and c.1043A>T [p.Asn348Ile]; c.425+1G>A/c.1043A>T [p.Asn348Ile]) and two homozygous (c.851C>G [p.Ser284]; c.350G>A [p.Gly114Arg]) variants in six individuals. These 10 SUN5 variants were found in 8 of 17 unrelated men, explaining the genetic defect in 47.06% of the affected individuals in our cohort. These variants were absent in 100 fertile population-matched control individuals. SUN5 variants lead to absent, significantly reduced, or truncated SUN5, and certain variants altered SUN5 distribution in the head-tail junction of the sperm. In summary, these results demonstrate that biallelic SUN5 mutations cause male infertility due to autosomal-recessive acephalic spermatozoa syndrome.

MeSH terms

  • Alleles*
  • Case-Control Studies
  • Computer Simulation
  • Exome / genetics
  • Female
  • Genes, Recessive / genetics*
  • Heterozygote
  • Homozygote
  • Humans
  • Infertility, Male / genetics*
  • Infertility, Male / metabolism
  • Infertility, Male / pathology
  • Male
  • Membrane Proteins
  • Mutation*
  • Pedigree
  • Proteins / genetics*
  • Spermatozoa / metabolism
  • Spermatozoa / pathology*
  • Syndrome


  • Membrane Proteins
  • Proteins
  • SUN5 protein, human