Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility.
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.
Dieterich
Klaus
K
Centre Hospitalier Universitaire (CHU) de Grenoble, Département de Génétique et Procréation, Unite Fonctionelle (UF) de biochimie génétique et moléculaire, F-38700 La Tronche, France.
Soto Rifo
Ricardo
R
Faure
Anne Karen
AK
Hennebicq
Sylviane
S
Ben Amar
Baha
B
Zahi
Mohamed
M
Perrin
Julia
J
Martinez
Delphine
D
Sèle
Bernard
B
Jouk
Pierre-Simon
PS
Ohlmann
Théophile
T
Rousseaux
Sophie
S
Lunardi
Joel
J
Ray
Pierre F
PF
D064108:Aurora Kinase C; D064127:Aurora Kinases; D001483:Base Sequence; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013077:Sperm Head / Q000737:chemistry*
C576927:AURKC protein, human; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases