I-38: Search for Genetic Causes of Male Infertility

Background: We are convinced that better infertility treatment will only be achieved with a better under understanding of the molecular mechanisms specific to each patient. To that effect we want to indentify genes involved in male infertility. Materials and Methods: We screened cohorts of infertile men to identify the cause of their infertility. Results: Our team has identified and caracterized several genes implicated in the genesis of two form of maleinfertility: macrozoospermia and globozoospermia. We showed that mutations in AURKC were responsible for macrozoospermia and that a homozygous deletion of the DPY19L2 was found in approximately 70% of globozoospermia patients. Before the characterization of these two genes the microdeletion of the Y chromosome were the only genetic defects described to alter spermatogenesis. We showed that AURKC deletions were are approximately as frequent in infertile men of North African descent as the Y chromosome microdeletions. We showed that Dpy19l2 is part of a new family of proteins permiting to establish a link between the nucleus and different organelles in the cytoplasm. Conclusion: The strategy of homozygocity mapping and exome sequencing has allowed us to identify several genes responsible for different infertility phenotype. We are convinced that many more genes will be identified in the near future.