title: Mutations of the aurora kinase C gene causing macrozoospermia are the most frequent genetic cause of male infertility in Algerian men.
abstract: Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C (AURKC) and DPY19L2 are now recommended for patients presenting macrozoospermia and globozoospermia, respectively, two rare forms of teratozoospermia particularly frequent among North African men. We carried out genetic analyses on Algerian patients, to evaluate the prevalence of these syndromes in this population and to compare it with the expected frequency of Klinefelter syndrome and Y-microdeletions. We carried out a retrospective study on 599 consecutive patients consulting for couple infertility at the assisted reproduction unit of the Ibn Rochd Clinique, Constantine, Algeria. Abnormal sperm parameters were observed in 404 men. Fourteen and seven men had typical macrozoospermia and globozoospermia profiles, respectively. Molecular diagnosis was carried out for these patients, for the AURKC and DPY19L2 genes. Eleven men with macrozoospermia had a homozygous AURKC mutation (79%), corresponding to 2.7% of all patients with abnormal spermograms. All the men with globozoospermia studied (n = 5), corresponding to 1.2% of all infertile men, presented a homozygous DPY19L2 deletion. By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion. Our findings thus indicate that AURKC mutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. Furthermore, we estimate that AURKC and DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.
authors.forename: Leyla
authors.initials: L
authors.lastname: Ounis
authors.forename: Abdelali
authors.initials: A
authors.lastname: Zoghmar
authors.forename: Charles
authors.initials: C
authors.lastname: Coutton
authors.forename: Leila
authors.initials: L
authors.lastname: Rouabah
authors.forename: Maroua
authors.initials: M
authors.lastname: Hachemi
authors.forename: Delphine
authors.initials: D
authors.lastname: Martinez
authors.forename: Guillaume
authors.initials: G
authors.lastname: Martinez
authors.forename: Ines
authors.initials: I
authors.lastname: Bellil
authors.forename: Douadi
authors.initials: D
authors.lastname: Khelifi
authors.forename: Christophe
authors.initials: C
authors.lastname: Arnoult
authors.forename: Julien
authors.initials: J
authors.lastname: Fauré
authors.forename: Sebti
authors.initials: S
authors.lastname: Benbouhedja
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Rouabah
authors.affiliation: Université Grenoble Alpes; Equipe Génétique Epigénétique et Thérapies de l'Infertilité, CNRS, AGIM; Laboratoire de Biochimie et Génétique Moléculaire, CHU Grenoble, Grenoble, France, .
authors.forename: Pierre F
authors.initials: PF
authors.lastname: Ray
mesh_terms: D000328:Adult; D000462:Algeria; D064108:Aurora Kinase C / Q000235:genetics*; D006801:Humans; D007248:Infertility, Male / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies; D013076:Sperm Count; D013077:Sperm Head / Q000473:pathology; D020554:Sperm Injections, Intracytoplasmic; D013081:Sperm Motility; D013082:Sperm Tail / Q000473:pathology; D013094:Spermatozoa / Q000002:abnormalities* / Q000473:pathology
chemical_list: C511317:DPY19L2 protein, human; D008565:Membrane Proteins; C576927:AURKC protein, human; D064108:Aurora Kinase C