The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population.
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.
Dieterich
Klaus
K
Département de Génétique et Procréation, CHU de Grenoble, Grenoble Cedex 9, France.
Zouari
Raoudha
R
Harbuz
Radu
R
Vialard
François
F
Martinez
Delphine
D
Bellayou
Hanane
H
Prisant
Nadia
N
Zoghmar
Abdelali
A
Guichaoua
Marie Roberte
MR
Koscinski
Isabelle
I
Kharouf
Mahmoud
M
Noruzinia
Mehrdad
M
Nadifi
Sellama
S
Sefiani
Abdelaziz
A
Lornage
Jacqueline
J
Zahi
Mohamed
M
Viville
Stéphane
S
Sèle
Bernard
B
Jouk
Pierre-Simon
PS
Jacob
Marie-Christine
MC
Escalier
Denise
D
Nikas
Yorgos
Y
Hennebicq
Sylviane
S
Lunardi
Joël
J
Ray
Pierre F
PF
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
C576927:AURKC protein, human; D064108:Aurora Kinase C; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases