Genetic analyses of a large cohort of infertile patients with globozoospermia, DPY19L2 still the main actor, GGN confirmed as a guest player - Archive ouverte HAL Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Genetic analyses of a large cohort of infertile patients with globozoospermia, DPY19L2 still the main actor, GGN confirmed as a guest player

Tristan Celse 1, 2 Caroline Cazin 1, 2 Flore Mietton 2 Guillaume Martinez 1 Delphine Martinez 2 Nicolas Thierry-Mieg 3 Amandine Septier 3 Catherine Metzler-Guillemain 4, 5 Julie Beurois 1 Antoine Clergeau 6 Selima Fourati Ben Mustapha 7 Mahmoud Kharouf 7 Abdelali Zoghmar 8 Ahmed Chargui 9 Aline Papaxanthos 10 Béatrice Dorphin 11 Bernard Foliguet 12 Chema Triki Christophe Sifer 13 Dominique Lauton 14 Gérard Tachdjian 15 Gilles Schuler Hervé Lejeune 16 Jacques Puechberty 17 Julien Bessonnat 2 Laurent Pasquier 18 Lionel Mery 19 Marine Poulain 20 Myriam Chaabouni 7 Nathalie Sermondade 21 Rosalie Cabry 22 Sebti Benbouhadja 8 Ségolène Veau 18 Cynthia Frapsauce 23 Valérie Mitchell Vincent Achard 24, 25 Veronique Satre 1 Sylviane Hennebicq 2 Raoudha Zouari 24 Christophe Arnoult 1 Zine-Eddine Kherraf 1 Charles Coutton 1 Pierre Ray 1
3 TIMC-BCM - Biologie Computationnelle et Modélisation
TIMC - Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525
Abstract : Globozoospermia is a rare phenotype of primary male infertility inducing the production of round-headed spermatozoa without acrosome. Anomalies of DPY19L2 account for 50-70% of all cases and the entire deletion of the gene is by far the most frequent defect identified. Here, we present a large cohort of 69 patients with 20-100% 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 eight novel and three already published mutations. 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 diagnosis efficiency rose to 77% for patients with > 50% of globozoospermia. In addition, results from whole-exome sequencing were scrutinized for 23 patients with a DPY19L2 negative diagnosis, searching for deleterious variants in the nine other genes described to be associated with globozoospermia in human (C2CD6, C7orf61, CCDC62, CCIN, DNAH17, GGN, PICK1, SPATA16, and ZPBP1). Only one homozygous novel truncating variant was identified in the GGN gene in one patient, 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 as well as in the other previously described candidate genes.
Liste complète des métadonnées

https://hal.archives-ouvertes.fr/hal-03025179
Contributeur : Nicolas Thierry-Mieg <>
Soumis le : jeudi 11 mars 2021 - 13:28:12
Dernière modification le : vendredi 11 juin 2021 - 13:20:05

Fichier

Celse 2020.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

Citation

Tristan Celse, Caroline Cazin, Flore Mietton, Guillaume Martinez, Delphine Martinez, et al.. Genetic analyses of a large cohort of infertile patients with globozoospermia, DPY19L2 still the main actor, GGN confirmed as a guest player. Human Genetics, Springer Verlag, 2021, Molecular Genetics of Male Infertility, 140 (1), pp.43-57. ⟨10.1007/s00439-020-02229-0⟩. ⟨hal-03025179⟩

Partager

Métriques

Consultations de la notice

225

Téléchargements de fichiers

134