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Master Thesis

Investigations génétiques d’une large cohorte de patients infertiles avec globozoospermie, implication du gène DPYL19L2 et proposition d'une nouvelle stratégie de diagnostic génétique

Abstract : Globozoospermia is a rare phenotype of primary male infertility inducing the production of a large proportion of round-headed spermatozoa without acrosome. Anomalies of the DPY19L2 gene account for 50 to 70% of all cases and the entire deletion of the gene is the main defect identified. We present here a large cohort of 69 patients with 20% to 100% of globozoospermia. Genetic analyses including multiplex ligation-dependent probe amplification, Sanger sequencing and whole exome sequencing identified 25 subjects with a homozygous DPY19L2 deletion (36%) and 14 carrying other DPY19L2 defects (20%). Overall, 11 deleterious single nucleotide variants were identified including 8 novel and 3 already published variants. Patients with a higher rate of round-headed spermatozoa were more often diagnosed and had a higher proportion of loss of function anomalies, highlighting a good genotype phenotype correlation. No gene defects were identified in patients carrying <50% of globozoospermia while the diagnosis efficiency rose to 77% for patients with >50% of globozoospermia. Nine other genes (PICK1, ZPBP1, SPATA16, CCDC62, C2CD6, CCIN, C7orf61, DNAH17 and GGN) have been previously described to be associated with human globozoospermia but defects in these genes have only been identified in a handful of patients. Interestingly we identified one patient with a homozygous novel truncating variant in GGN confirming the association of GGN with globozoospermia. In view of these results, we propose a novel diagnostic strategy focusing on patients with at least 50% of globozoospermia and based on a classical qualitative PCR to detect DPY19L2 homozygous deletions. In the absence of the latter, we recommend to perform whole exome sequencing to search for defects in DPY19L2 and in other candidate genes.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03027534
Contributor : Jean-Hugues Morneau <>
Submitted on : Friday, November 27, 2020 - 11:00:23 AM
Last modification on : Sunday, November 29, 2020 - 3:15:13 AM
Long-term archiving on: : Sunday, February 28, 2021 - 6:59:24 PM

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  • HAL Id : dumas-03027534, version 1

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Tristan Celse. Investigations génétiques d’une large cohorte de patients infertiles avec globozoospermie, implication du gène DPYL19L2 et proposition d'une nouvelle stratégie de diagnostic génétique. Médecine humaine et pathologie. 2020. ⟨dumas-03027534⟩

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