Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility

Nat Genet. 2007 May;39(5):661-5. doi: 10.1038/ng2027. Epub 2007 Apr 15.

Abstract

The World Health Organization conservatively estimates that 80 million people suffer from infertility worldwide. Male factors are believed to be responsible for 20-50% of all infertility cases, but microdeletions of the Y chromosome are the only genetic defects altering human spermatogenesis that have been reported repeatedly. We focused our work on infertile men with a normal somatic karyotype but typical spermatozoa mainly characterized by large heads, a variable number of tails and an increased chromosomal content (OMIM 243060). We performed a genome-wide microsatellite scan on ten infertile men presenting this characteristic phenotype. In all of these men, we identified a common region of homozygosity harboring the aurora kinase C gene (AURKC) with a single nucleotide deletion in the AURKC coding sequence. In addition, we show that this founder mutation results in premature termination of translation, yielding a truncated protein that lacks the kinase domain. We conclude that the absence of AURKC causes male infertility owing to the production of large-headed multiflagellar polyploid spermatozoa.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase C
  • Aurora Kinases
  • Base Sequence
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infertility, Male / genetics*
  • Male
  • Microsatellite Repeats / genetics
  • Molecular Sequence Data
  • Pedigree
  • Point Mutation / genetics*
  • Polyploidy*
  • Protein-Serine-Threonine Kinases / genetics*
  • Sperm Head / chemistry*

Substances

  • AURKC protein, human
  • Aurora Kinase C
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases

Associated data

  • RefSeq/NM_00101587
  • RefSeq/NP_001015878