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Basic Clin Androl. 2019 Mar 4;29:2. doi: 10.1186/s12610-019-0083-9. eCollection 2019.

Genetic causes of male infertility: snapshot on morphological abnormalities of the sperm flagellum.

Author information

1INSERMU1016, CNRS UMR8104, Université Paris Descartes, 75014 Paris, France.
2Centre National de la Recherche Scientifique UMR8104, 75014 Paris, France.
3Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
Institut for Advanced Biosciences, Université Grenoble Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France.
5CHU Grenoble Alpes, UM de Génétique Chromosomique, Grenoble, France.
CHU de Grenoble, UM GI-DPI, F-38000 Grenoble, France.


in English, French

Male infertility due to Multiple Morphological Abnormalities of the sperm Flagella (MMAF), is characterized by nearly total asthenozoospermia due to the presence of a mosaic of sperm flagellar anomalies, which corresponds to short, angulated, absent flagella and flagella of irregular calibre. In the last four years, 7 novel genes whose mutations account for 45% of a cohort of 78 MMAF individuals were identified: DNAH1, CFAP43, CFAP44, CFAP69, FSIP2, WDR66 (CFAP251), AK7. This successful outcome results from the efficient combination of high-throughput sequencing technologies together with robust and complementary approaches for functional validation, in vitro, and in vivo using the mouse and unicellular model organisms such as the flagellated parasite T. brucei. Importantly, these genes are distinct from genes responsible for Primary Ciliary Dyskinesia (PCD), an autosomal recessive disease associated with both respiratory cilia and sperm flagellum defects, and their mutations therefore exclusively lead to male infertility. In the future, these genetic findings will definitely improve the diagnosis efficiency of male infertility and might provide genotype-phenotype correlations, which could be helpful for the prognosis of intracytoplasmic sperm injection (ICSI) performed with sperm from MMAF patients. In addition, functional study of these novel genes should improve our knowledge about the protein networks and molecular mechanisms involved in mammalian sperm flagellum structure and beating.


AK; CFAP; DNAH; Genetic; MMAF; Male infertility; Sperm; WDR

Conflict of interest statement

Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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