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Bi-allelic Mutations in ARMC2 Lead to Severe Astheno-Teratozoospermia Due to Sperm Flagellum Malformations in Humans and Mice

dc.rights.licenseopenen_US
dc.contributor.authorCOUTTON, C.
dc.contributor.authorMARTINEZ, G.
dc.contributor.authorKHERRAF, Z.-E.
dc.contributor.authorAMIRI-YEKTA, A.
dc.contributor.authorBOGUENET, M.
dc.contributor.authorSAUT, A.
dc.contributor.authorHE, X.
dc.contributor.authorZHANG, F.
dc.contributor.authorCRISTOU-KENT, M.
dc.contributor.authorESCOFFIER, J.
dc.contributor.authorBIDART, M.
dc.contributor.authorSATRE, V.
dc.contributor.authorCONNE, B.
dc.contributor.authorFOURATI BEN MUSTAPHA, S.
dc.contributor.authorHALOUANI, L.
dc.contributor.authorMARRAKCHI, O.
dc.contributor.authorMAKNI, M.
dc.contributor.authorLATROUS, H.
dc.contributor.authorKHAROUF, M.
dc.contributor.authorPERNET-GALLAY, K.
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBONHIVERS, M.
dc.contributor.authorHENNEBICQ, S.
dc.contributor.authorDULIOUST, E.
dc.contributor.authorTOURÉ, A.
dc.contributor.authorRIVES, N.
dc.contributor.authorGOURABI, H.
dc.contributor.authorCAO, Y.
dc.contributor.authorZOUARI, R.
dc.contributor.authorHOSSEINI, S. H.
dc.contributor.authorNEF, S.
dc.contributor.authorTHIERRY-MIEG, N.
dc.contributor.authorARNOULT, C.
dc.contributor.authorRAY, P.
dc.date.accessioned2023-06-14T10:53:02Z
dc.date.available2023-06-14T10:53:02Z
dc.date.issued2019-01
dc.identifier.issn0002-9297en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182684
dc.description.abstractEnMale infertility is a major health concern. Among its different causes, multiple morphological abnormalities of the flagella (MMAF) induces asthenozoospermia and is one of the most severe forms of qualitative sperm defects. Sperm of affected men display short, coiled, absent, and/or irregular flagella. To date, six genes (DNAH1, CFAP43, CFAP44, CFAP69, FSIP2, and WDR66) have been found to be recurrently associated with MMAF, but more than half of the cases analyzed remain unresolved, suggesting that many yet-uncharacterized gene defects account for this phenotype. Here, whole-exome sequencing (WES) was performed on 168 infertile men who had a typical MMAF phenotype. Five unrelated affected individuals carried a homozygous deleterious mutation in ARMC2, a gene not previously linked to the MMAF phenotype. Using the CRISPR-Cas9 technique, we generated homozygous Armc2 mutant mice, which also presented an MMAF phenotype, thus confirming the involvement of ARMC2 in human MMAF. Immunostaining experiments in AMRC2-mutated individuals and mutant mice evidenced the absence of the axonemal central pair complex (CPC) proteins SPAG6 and SPEF2, whereas the other tested axonemal and peri-axonemal components were present, suggesting that ARMC2 is involved in CPC assembly and/or stability. Overall, we showed that bi-allelic mutations in ARMC2 cause male infertility in humans and mice by inducing a typical MMAF phenotype, indicating that this gene is necessary for sperm flagellum structure and assembly.
dc.description.sponsorshipGénétique et Physiopathologie des anomalies morphologiques du flagelle spermatique associé à une infertilité masculine.en_US
dc.language.isoENen_US
dc.subject.enCilia
dc.subject.enInfertility
dc.subject.enFlagella
dc.subject.enSpermatozoa
dc.subject.enMultiple morphological anomalies of the flagella (MMAF)
dc.subject.enSpermatogenesis
dc.title.enBi-allelic Mutations in ARMC2 Lead to Severe Astheno-Teratozoospermia Due to Sperm Flagellum Malformations in Humans and Mice
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.ajhg.2018.12.013en_US
dc.subject.halSciences du Vivant [q-bio]/Génétique/Génétique humaineen_US
dc.subject.halSciences du Vivant [q-bio]/Bio-Informatique, Biologie Systémique [q-bio.QM]en_US
dc.subject.halSciences du Vivant [q-bio]/Biologie de la reproductionen_US
bordeaux.journalAmerican Journal of Human Geneticsen_US
bordeaux.page331-340en_US
bordeaux.volume104en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue2en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-02003335
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=American%20Journal%20of%20Human%20Genetics&rft.date=2019-01&rft.volume=104&rft.issue=2&rft.spage=331-340&rft.epage=331-340&rft.eissn=0002-9297&rft.issn=0002-9297&rft.au=COUTTON,%20C.&MARTINEZ,%20G.&KHERRAF,%20Z.-E.&AMIRI-YEKTA,%20A.&BOGUENET,%20M.&rft.genre=article


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