Macrozoospermia: screening for the homozygous c.144delC mutation in AURKC gene in infertile men and estimation of its heterozygosity frequency in the Tunisian population
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Macrozoospermia is a rare condition of male infertility characterized by the presence of close to 100 % large-headed multiflagellar spermatozoa. The homozygous mutation (c.144delC) in aurora kinase C gene (AURKC) has been identified as the most frequent mutation causing macrozoospermia in North African patients. The aim of this study was to evaluate the prevalence of this condition in Tunisia and estimate the frequency of c.144delC mutation among infertile and control populations.
Sequencing c.144delC mutation was carried out in 33 macrozoospermic patients among 6652 infertile men. Minisequencing of exon3 was performed in 250 unrelated control individuals to estimate the frequency of c.144delC heterozygosity.
More than 80 % of macrozoospermic patients were c.144delC homozygous. The prevalence of homozygous c.144delC was 0.4 % among infertile men (27/6652). The frequency of heterozygosity was 0.4 % among controls (1/250). Surprisingly, it is five times less common than established in the general population of North Africa (2 %) or in the Moroccan population (1.7 %).
We show that this mutation is relatively less frequent in the Tunisian population than in other Maghrebian populations. The occurrence of homozygous mutation among infertile men can be attributed to the high rate of consanguinity and its impact on the expression of this autosomal recessive male infertility disorder rather than a high frequency of heterozygous carriers among the general population. This highlights the importance of the molecular analysis of AURKC mutations for infertile men with high percentage of large-headed multiflagellar spermatozoa in order to limit unnecessary in vitro fertilization attempts for them.
KeywordsMale infertility Macrozoospermia AURKC mutations Tunisia
The authors appreciate the cooperation and generosity of all patients and control individuals. We would like to thank Pr. Khaled Khadim-Allah, English Professor at the Faculty of Medicine Ibn Eljazzar (Sousse) for his revisions of the manuscript. We also appreciate the expert technical assistance of Hajer Farroukh, Lamia Hammami, Khaled Chabbah, Ahlem Msakni, Sihem Sassi, and Safa Bouker.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare that they have no competing interests.
- 5.Ben Khelifa M, Coutton C, Zouari R, Karaouzene T, Rendu J, Bidart M, et al. Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella. Am J Hum Genet. 2014;94(1):95–104. doi: 10.1016/j.ajhg.2013.11.017.PubMedCentralCrossRefPubMedGoogle Scholar
- 6.Perrin A, Morel F, Moy L, Colleu D, Amice V, DeBraekeleer M. Study of aneuploidy in large-headed, multiple-tailed spermatozoa: case report and review of the literature. Fertil Steril. 2008;90(4):1201 e13–7. doi: 10.1016/j.fertnstert.2007.09.013S0015-0282(07)03557-1.CrossRefPubMedGoogle Scholar
- 7.Achard V, Paulmyer-Lacroix O, Mercier G, Porcu G, Saias-Magnan J, Metzler-Guillemain C, et al. Reproductive failure in patients with various percentages of macronuclear spermatozoa: High level of aneuploid and polyploid spermatozoa. J Androl. 2007;28(4):600–6. doi: 10.2164/jandrol.106.001933.CrossRefPubMedGoogle Scholar
- 17.Ounis L, Zoghmar A, Coutton C, Rouabah L, Hachemi M, Martinez D, et al. Mutations of the aurora kinase C gene causing macrozoospermia are the most frequent genetic cause of male infertility in Algerian men. Asian J Androl. 2015;17(1):68–73. doi: 10.4103/1008-682X.136441.PubMedCentralCrossRefPubMedGoogle Scholar
- 19.WHO. (World Health Organization). Laboratory manual for the examination and processing of human semen. 5th ed. New York: Cambridge University Press; 2010.Google Scholar
- 25.El Kerch F, Lamzouri A, Laarabi FZ, Zahi M, Ben Amar B, Sefiani A. Confirmation of the high prevalence in Morocco of the homozygous mutation c.144delC in the aurora kinase C gene (AURKC) in the teratozoospermia with large-headed spermatozoa. J Gynecol Obstet Biol Reprod. 2011;40(4):329–33. doi: 10.1016/j.jgyn.2010.09.003.CrossRefGoogle Scholar