title: The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population.
abstract: Infertility concerns a minimum of 70 million couples worldwide. An important proportion of cases is believed to have a genetic component, yet few causal genes have been identified so far. In a previous study, we demonstrated that a homozygous mutation (c.144delC) in the Aurora Kinase C (AURKC) gene led to the production of large-headed polyploid multi-flagellar spermatozoa, a primary infertility phenotype mainly observed in North Africans. We now want to estimate the prevalence of the defect, to improve our understanding of AURKC physiopathology in spermatogenesis and assess its implication in oogenesis. A carrier frequency of 1/50 was established from individuals from the Maghrebian general population, comparable to that of Y-microdeletions, thus far the only known recurrent genetic event altering spermatogenesis. A total of 62 patients were genotyped, all who had a typical phenotype with close to 100% large-headed spermatozoa were homozygously mutated (n = 32), whereas no AURKC mutations were detected in the others. Two homozygous females were identified; both were fertile indicating that AURKC is not indispensible in oogenesis. Previous FISH results had showed a great chromosomal heterogeneity in these patient's spermatozoa. We demonstrate here by flow cytometry that all spermatozoa have in fact a homogeneous 4C DNA content and are thus all blocked before the first meiotic division. Our data thus indicate that a functional AURKC protein is necessary for male meiotic cytokinesis while its absence does not impair oogenesis.
authors.affiliation: Département de Génétique et Procréation, CHU de Grenoble, Grenoble Cedex 9, France.
authors.forename: Klaus
authors.initials: K
authors.lastname: Dieterich
authors.forename: Raoudha
authors.initials: R
authors.lastname: Zouari
authors.forename: Radu
authors.initials: R
authors.lastname: Harbuz
authors.forename: François
authors.initials: F
authors.lastname: Vialard
authors.forename: Delphine
authors.initials: D
authors.lastname: Martinez
authors.forename: Hanane
authors.initials: H
authors.lastname: Bellayou
authors.forename: Nadia
authors.initials: N
authors.lastname: Prisant
authors.forename: Abdelali
authors.initials: A
authors.lastname: Zoghmar
authors.forename: Marie Roberte
authors.initials: MR
authors.lastname: Guichaoua
authors.forename: Isabelle
authors.initials: I
authors.lastname: Koscinski
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Kharouf
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Noruzinia
authors.forename: Sellama
authors.initials: S
authors.lastname: Nadifi
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Sefiani
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lornage
authors.forename: Mohamed
authors.initials: M
authors.lastname: Zahi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Viville
authors.forename: Bernard
authors.initials: B
authors.lastname: Sèle
authors.forename: Pierre-Simon
authors.initials: PS
authors.lastname: Jouk
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Jacob
authors.forename: Denise
authors.initials: D
authors.lastname: Escalier
authors.forename: Yorgos
authors.initials: Y
authors.lastname: Nikas
authors.forename: Sylviane
authors.initials: S
authors.lastname: Hennebicq
authors.forename: Joël
authors.initials: J
authors.lastname: Lunardi
authors.forename: Pierre F
authors.initials: PF
authors.lastname: Ray
mesh_terms: D000352:Africa, Northern; D064108:Aurora Kinase C; D064127:Aurora Kinases; D044383:Black People / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005298:Fertility; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013091:Spermatogenesis; D013094:Spermatozoa / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D014019:Tissue Donors
chemical_list: C576927:AURKC protein, human; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases