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Biallelic variants in MAATS1 encoding CFAP91, a calmodulin-associated and spoke-associated complex protein, cause severe astheno-teratozoospermia and male infertility

dc.contributor.authorMARTINEZ, Guillaume
dc.contributor.authorBEUROIS, Julie
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorDACHEUX, Denis
IDREF: 230332838
dc.contributor.authorCAZIN, Caroline
dc.contributor.authorBIDART, Marie
dc.contributor.authorKHERRAF, Zine-Eddine
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorROBINSON, Derrick
dc.contributor.authorSATRE, Véronique
dc.contributor.authorLE GAC, Gerald
dc.contributor.authorKA, Chandran
dc.contributor.authorGOURLAOUEN, Isabelle
dc.contributor.authorFICHOU, Yann
dc.contributor.authorPETRE, Graciane
dc.contributor.authorDULIOUST, Emmanuel
dc.contributor.authorZOUARI, Raoudha
dc.contributor.authorTHIERRY-MIEG, Nicolas
dc.contributor.authorTOURÉ, Aminata
dc.contributor.authorARNOULT, Christophe
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBONHIVERS, Mélanie
dc.contributor.authorRAY, Pierre
dc.contributor.authorCOUTTON, Charles
dc.date.accessioned2023-06-05T07:13:49Z
dc.date.available2023-06-05T07:13:49Z
dc.date.issued2020-10
dc.identifier.issn0022-2593
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182468
dc.description.abstractEnBackground: Multiple morphological abnormalities of the flagella (MMAF) consistently lead to male infertility due to a reduced or absent sperm motility defined as asthenozoospermia. Despite numerous genes recently described to be recurrently associated with MMAF, more than half of the cases analysed remain unresolved, suggesting that many yet uncharacterised gene defects account for this phenotype METHODS: Exome sequencing was performed on 167 infertile men with an MMAF phenotype. Immunostaining and transmission electron microscopy (TEM) in sperm cells from affected individuals were performed to characterise the ultrastructural sperm defects. Gene inactivation using RNA interference (RNAi) was subsequently performed in Trypanosoma.Results: We identified six unrelated affected patients carrying a homozygous deleterious variants in MAATS1, a gene encoding CFAP91, a calmodulin-associated and spoke-associated complex (CSC) protein. TEM and immunostaining experiments in sperm cells showed severe central pair complex (CPC) and radial spokes defects. Moreover, we confirmed that the WDR66 protein is a physical and functional partner of CFAP91 into the CSC. Study of Trypanosoma MAATS1's orthologue (TbCFAP91) highlighted high sequence and structural analogies with the human protein and confirmed the axonemal localisation of the protein. Knockdown of TbCFAP91 using RNAi impaired flagellar movement led to CPC defects in Trypanosoma as observed in humans.Conclusions: We showed that CFAP91 is essential for normal sperm flagellum structure and function in human and Trypanosoma and that biallelic variants in this gene lead to severe flagellum malformations resulting in astheno-teratozoospermia and primary male infertility.
dc.description.sponsorshipLa protéine TAT1 (SLC26A8), partenaire et activateur de CFTR dans le spermatozoïde, au carrefour des infertilités masculines et de la mucoviscidose.
dc.description.sponsorshipAlliance française contre les maladies parasitaires - ANR-11-LABX-0024
dc.description.sponsorshipDéveloppment d'une infrastructure française distribuée coordonnée - ANR-10-INBS-0004
dc.language.isoen
dc.publisherBMJ Publishing Group
dc.subject.engenetics
dc.subject.enmolecular genetics
dc.subject.enreproductive medicine
dc.title.enBiallelic variants in MAATS1 encoding CFAP91, a calmodulin-associated and spoke-associated complex protein, cause severe astheno-teratozoospermia and male infertility
dc.typeArticle de revueen_US
dc.identifier.doi10.1136/jmedgenet-2019-106775
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalJournal of Medical Geneticsen_US
bordeaux.page708-716
bordeaux.volume57
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue10
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
bordeaux.import.sourcehal
hal.identifierhal-03004959
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
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